Category Archives: Pennsylvania Stem Cells

Kyle Orwig, professor in the Department of Obstetrics, Gynecology and Reproductive Sciences in the School of Medicine, was awarded theDistinguished Researcher Award from the American Society for Reproductive Medicine (ASRM)for his outstanding contributions to the field through clinical or basic reproduction research published over the last decade.

He will be recognized for this achievement during the presidents gala and opening ceremony of the ASRM 2022 Scientific Congress on Monday, Oct. 24, in Anaheim, California, and present during the 2023 Annual Meeting of the Society for the Study of Reproduction.

Orwig was recruited to join Magee-Womens Research Institute and Pitt as a tenure track professor in 2003 following his postdoctoral and junior faculty position at the University of Pennsylvania, where he studied stem cells and spermatogenesis, or sperm cell development.

Orwig directs the UPMC Fertility Preservation Program and the UPMC Magee Center for Reproduction and Transplantation. His research lab focuses on germ lineage development, stem cells, fertility and infertility, and treatment of the latter. Located in the Magee-Women Research Institute and Magee-Womens Hospital, the Orwig Lab has received funding from the National Institutes of Health, the Sylvia Bernassoli Fund (started by a Magee-Womens Hospital nurse who donated a substantial portion of her retirement savings to support infertility research), the Richard King Mellon Foundation and others.

Orwig currently serves as an ASRM Research Institute Advisory Committee Chair and has had work published more than 100 times in a leading biomedical database.

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Kyle Orwig received the Distinguished Researcher Award from the American Society for Reproductive Medicine - University of Pittsburgh

By Ed Miseta, Chief Editor, Clinical LeaderFollow Me On Twitter @EdClinical

Most folks know that your life can change in an instant. For example, the moment you meet someone that you just know is meant to be your soul mate, the moment you found out you would be a parent, or the day you started a new job that you wanted your entire life. But other times your life can change in unpleasant ways, and that happened to me last year.

It started innocently enough. It was a nice spring day in May 2021. I remember it well because I am from Erie, Pennsylvania and we do not get many nice spring days in May. The previous fall I had cut down a couple bushes in my yard and that day I hoped to dig out the stumps. I had my saw, shovel, and pick, and used them to chop, dig, and cut through the roots. It took about two hours, but I managed to get them out.

The next day I was in a lot of pain, which I expected. It was the first yard work I had done in seven months, and I know I am not getting any younger. I decided to take it easy for a few days and assumed the pain would go away.

Unfortunately, it did not go away. And it did not get better. In fact, after a few weeks, I could tell the pains were getting worse. I had pain in my left shoulder that I was convinced was a torn rotator cuff muscle. I also had pain in my left side and severe pain in my lower back. The pain in my back got so bad I could barely sit for more than a few minutes. I also had pain in my right leg that worsened until I was forced to walk with a noticeable limp.

After a few weeks I did go to see my primary care provider. I was convinced the pain was muscle related, although my doctor felt it was bone related. When x-rays showed no bone damage, he sent me for a scan to see what might be causing the leg pain. I went to the hospital on Friday July 2nd to get the scan done, but on that day, I looked really bad. In fact, when I was checking out, the nurse I spoke to was so concerned about my condition she sent me to the emergency room to be checked out.

Tests Lead To More Tests

They put me in a bed, started an IV, and began the requisite blood work. The first thing they noticed was that my kidney function was almost non-existent. I had started taking NSAIDs for the pain. When they did not help, I started taking more. What I did not realize is that even when those medications are not helping with your pain, they can be damaging your kidneys. They also found that my calcium levels were sky high. A doctor decided they would admit me to the hospital. So much for my 4th of July plans.

They needed to run a lot more tests, but a holiday weekend is not the best time to do that. Over the weekend they focused on getting my kidneys back on track, and on Tuesday they were back to running tests.

On Thursday, a cancer doctor came in and told me he saw spots on one of the scans. Those spots, coupled with the pain I was experiencing, led him to believe they might be lytic lesions that are associated with a blood cancer called multiple myeloma. The physician stated he would have to perform a bone marrow biopsy, which he did later that afternoon. The next day he came into my room and told my wife and I that the biopsy confirmed his diagnosis.

To say that was a shocking moment in my life would be a huge understatement. There was no history of multiple myeloma in my family. I tried to eat healthy, and I spent a lot of my free time running and biking. There was no way I could have cancer. But I did, and that evening I received my first chemo treatment. I continued to receive them at the cancer center in Erie for the next five months. During that time, my pain levels improved until I was able to walk and move with little discomfort. The pain in my lower back did not improve but after eight radiation treatments that pain subsided as well.

In December I went to the Roswell Cancer Center in Buffalo to have some stem cells removed. I went back in January to have a blast of chemo that would wipe out my bone marrow and to receive the stem cells they removed. That was followed by the four worst weeks of my life.

Thanks to the wonderful folks at Roswell, I recovered from that treatment as well. After a few months I began working from home and on June 6, 2022, I returned to working in the office for the first time since my diagnosis. I feel better than I have in a year and one week after returning to the office I also ran my first 5k in more than 15 months.

Why I Feel Thankful

By now you might be wondering why I have decided to share this story. I have been covering clinical trials for almost 10 years. In that time, I have developed a growing respect for everyone who works in this industry.

I have had the opportunity to speak to hundreds of clinical executives from sponsor companies. I have also seen and heard the passion they bring to their jobs every day. A few years ago, I interviewed an executive whose company was working on a treatment for a rare disease. During the interview she became emotional and at one point I could tell she was crying. Why the tears? Did they discover a cure for the disease? No. Were they able to improve the condition of patients? No. In fact, the condition of patients in the trial continued to decline.

However, the trial did cause the condition of patients to deteriorate at a slower rate than patients who did not receive the treatment. That is what caused her to be so emotional.

Some may not have understood her reaction, considering the results of the study. However, I am sure she knew that when you extend the life of a patient by one year, one month, or even one week, that is extra time the patient can spend with loved ones, take in a concert or sporting event, walk their dogs, or just sit outside and enjoy the sun. And I am sure that executive also knew that cures do not happen overnight. Drug discovery is a long and tedious process. A small advancement made by one company can lead to advancements by other companies that can eventually lead to an effective treatment or a cure. She knew the discoveries that had just been made were the first steps towards that treatment. That is why she was so emotional, and that is the passion that pharma folks bring to drug discovery every day.

Contributions of Partners

Pharma does amazing work to help patients, but they do not perform the work alone. Several partners assist them with the work. First, there are the sites. Without clinical sites and their qualified staff, trials could not be conducted. Sites know their patients and they recruit those individuals, treat them, and gather the data required to gain a regulatory approval.

Then there are the heroes we call patients. When it was time for me to start my chemo drugs, my oncologist was able to tell me they were FDA approved, how they would help my condition, and what side effects I was likely to experience. But as I was receiving those treatments, I thought about the patients who came before me. At one time, a group of patients were told they had multiple myeloma and there was no effective treatment. They were told a pharma company had a drug that might help their condition. The treatment was not FDA approved, we were not sure what the side effects would be, and in fact we were not even sure it would improve their condition. But we needed them to take part in a clinical trial to evaluate the drugs and see if they worked. Many of those patients thought about it and said, Sure, Ill do it. That is my definition of a hero.

Today I feel better because of their efforts. One of the chemo drugs I took, Velcade, did not exist 20 years ago. Another chemo treatment I received, and my current maintenance medication, is Revlimid, which has only been available to patients for five years. I feel thankful to those patients who helped make these treatments available for me.

There is one group I have not mentioned yet, and that is the contract research organizations (CROs). Everyone involved in drug development knows that drug discovery is not possible without the efforts of those partners. In todays clinical trials, CROs do most of the heavy lifting. A sponsor company can take a drug so far, and then hand it over to a CRO that will take it through a difficult Phase 3 trial and produce the package of information needed for regulatory approval. Drugs would not be approved for patients without their efforts, and I am thankful to those partners as well, who I suspect will rarely get the recognition they deserve.

Pharma does not have the best reputation, and much of the criticism the industry receives in not deserved. So, on behalf of myself and the millions of patients whose lives you have saved or improved, thank you. We appreciate the work you do.

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I Have Cancer And I'm Thankful For The Life Science Industry - Clinical Leader

That includes $10 million Republicans had included for marketing programs that promote adoption as an alternative to abortion, $2 million in tax credits for adoptive parents and $3 million for a maternal navigator pilot program that would be run by a nonprofit that promotes childbirth and alternatives to abortion.

Related:

Whitmer will also veto $1.5 million Republicans included for "pregnancy resource centers" and $700,000 for Real Alternatives, a Pennsylvania-based nonprofit that expanded into Michigan several years ago, according to her office.

Whitmer spokesperson Bobby Leddy accused such centers of using deceptive advertising that target young women and women with low incomes who are seeking abortion care, painting themselves as comprehensive, licensed health care clinics that provide all options, and then lie to women about medical facts.

Gov. Whitmer supports legislation that provides every possible resource to women who are pregnant, seeking to start a family, or those who arent ready yet, but she cannot support aspects of a bill that sends millions in taxpayer dollars to fake health centers that intentionally withhold information from women about their health, bodies, and full reproductive freedom, Leddy wrote in a statement.

Genevieve Marnon, who lobbied for the funding for Right to Life of Michigan, said she is not surprised by the expective vetoes but bristled at the governors rejection of what the Legislature envisioned as a $2 million tax credit program for adoptive parents.

We have the largest budget in history, and we want to throw a bone to adoptive parents, and she's vetoing that? Wow, she's for women alright, said Marnon, who is legislative director of the states Right to Life.

Marnon declined further comment until Whitmer explains her decision in an official veto letter.

The expected vetoes come as Whitmer continues to ask the Michigan Supreme Court to declare unconstitutional a 1931 law that would ban most abortions in the state. The Republican-led Legislature is defending the law, which was temporarily suspended in May but could be reactivated following the U.S. Supreme Court decision to strike down Roe v. Wade.

In signing the education portion of the state budget last week, Whitmer line-item vetoed $1 million for pregnant and parenting student support services at Michigan colleges that would be prohibited from referring students to abortion providers, along with $5 million for research grants prohibiting universities from using stem cells derived from aborted fetal tissue.

House Appropriations Chair Thomas Albert, who could not immediately be reached for comment Monday, responded to last weeks education vetoes by suggesting Whitmer is only interested in promoting the deadly choice that ends a human life."

"Its inexplicable that the governor would refuse to support pregnant community college students who choose to become parents," Albert told the Detroit Free Press.

Whitmer is expected to sign the second part of the state budget a nearly $55 billion general government spending plan later this week, minus the abortion and adoption-related provisions.

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Whitmer to veto adoption, abortion alternative funds from Michigan budget - Bridge Michigan

WARREN, N.J., July 07, 2022--(BUSINESS WIRE)--Tevogen Bio, a late stage clinical biotechnology company specializing in developing cell and gene therapies in oncology, neurology, and virology, today announced the appointment of preeminent oncologist Neal Flomenberg, M.D. as Chief Scientific Officer (CSO) and Global Head of Research and Development. Dr. Flomenberg will lead the companys diverse and rapidly advancing research and development initiatives of its highly adaptable precision T cell product pipeline in oncology, neurology, and virology.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20220707005531/en/

Acclaimed oncologist and immunotherapy expert, Neal Flomenberg, M.D. joins Tevogen Bio as Chief Scientific Officer and Global Head of R&D (Photo: Business Wire)

Most recently, Dr. Flomenberg served as Professor and Chairman of the Department of Medical Oncology and Deputy Director of Sidney Kimmel Cancer Center of Thomas Jefferson University & Hospital. Under his leadership, Jeffersons Department of Medical Oncology more than tripled in size, established a nationally recognized senior adult oncology program as well as an embedded Supportive Medicine and Survivorship Program. At Jefferson, Dr. Flomenberg also served as Director of the Hematologic Malignancies, Blood and Marrow Transplantation (BMT) Program.

Throughout his more than forty-year career, Dr. Flomenberg has maintained a longstanding interest in the immunogenetics and immunology of stem cell transplantation, with the goal of making transplantation safer and more widely available. As Chairman of Tevogens Scientific Advisory Board, he helped advance Tevogens lead investigational product, TVGN-489, through proof-of-concept clinical trial for treatment of high-risk COVID-19 patients. Trial enrollment is currently nearing completion.

Story continues

In his new capacity at Tevogen, Dr. Flomenberg will serve as member of the executive team and lead companys ambitious R&D initiatives, allowing for further advancement of its next generation precision T cell technology platforms. Dr. Flomenberg and his leadership team will operate out of Tevogens R&D Center located in Philadelphias Wanamaker building.

"There is no better person than Neal to lead the advancement of Tevogens highly promising genetically unmodified T cell technology platforms, which we believe will pave the way for the next era of personalized T cell therapeutics for large patient populations through convenience and affordability for the very first time," said Tevogen CEO Ryan Saadi, M.D., M.P.H. "A lifelong student of science, Neals compassionate nature, brilliant mind, and unwavering passion to innovate leading-edge medicines for the good of humanity are just a few of the characteristics that make him the ideal leader to realize the fullest potential of our R&D initiatives."

"I am thrilled to serve in this new role at Tevogen, a truly patient-centric company designed to achieve commercial success through its advanced science and efficient business model which ensure affordability. I have dedicated my career to increasing our understanding of blood cancers and the infections which plague these and other patient groups as well as the cellular immunologic approaches which might be used to address these problems," said Dr. Flomenberg. "Tevogens proprietary approach allows cellular immunotherapeutics to be developed with unprecedented specificity and precision while remaining affordable and broadly applicable. Applications range from acute viral infections such as COVID-19, to longer term consequences of infections such as Long-COVID and Multiple Sclerosis, to viral-induced and non-viral induced cancers," he added.

Dr. Flomenberg has been the recipient of numerous awards including: The Simon Gratz Award for Research Most Likely to influence Patient Care (2003), The Leukemia Lymphoma Society Contributions to Mankind Award (2006), The Pennsylvania State University Outstanding Science Alumnus Award (2006), Inaugural recipient of the Philadelphia Chapter of the Leukemia Lymphoma Societys Lifetime Achievement Award (2018), Thomas Jefferson Universitys Alumnus of the Year Award (2019), and Jeffersons Deans Lifetime Distinguished Service Award (2022).He received a Bachelor of Science degree from Penn State University and earned a Doctor of Medicine degree from Jefferson Medical College.

About Tevogens Next Generation Precision T Cell Platform

Tevogens next generation precision T cell platform is designed to provide increased specificity to eliminate malignant and virally infected cells, while allowing healthy cells to remain intact. Multiple targets are selected in advance with the goal of overcoming mutational capacity of cancer cells and viruses.

Tevogen is investigating its technologys potential to overcome the primary barriers to the broad application of personalized T cell therapies: potency, purity, production-at-scale, and patient-pairing, without the limitations of current approaches. Tevogens goal is to open the vast and unprecedented potential of developing personalized immunotherapies for large patient populations impacted by common cancers and viral infections.

The companys lead product, TVGN-489, is currently in clinical trial for high-risk COVID-19 patients at Jefferson University Hospitals in Philadelphia. TVGN-489 is a highly purified, genetically unmodified, off-the-shelf, allogeneic SARS-CoV-2-specific cytotoxic CD8+ T lymphocyte (CTL) product designed to detect targets spread across the entire viral genome.

Tevogen recently announced the initiation of the fourth and final dose level of its investigational T cell therapy for high-risk COVID-19 patients in the proof of concept clinical trial of TVGN-489. No dose limiting toxicities or treatment-related adverse events, including Cytokine Release Syndrome (CRS), have been observed to date in any of the dose cohorts.

About Tevogen Bio

Tevogen Bio is driven by a team of distinguished scientists and highly experienced biopharmaceutical leaders who have successfully developed and commercialized multiple franchises. Tevogens leadership believes that accessible personalized immunotherapies are the next frontier of medicine, and that disruptive business models are required to sustain medical innovation in the post-pandemic world.

Forward Looking Statements

This press release contains certain forward-looking statements relating to Tevogen Bio Inc (the "Company") and its business. These statements are based on managements current expectations and beliefs as of the date of this release and are subject to a number of factors which involve known and unknown risks, delays, uncertainties and other factors not under the Companys control that may cause actual results, performance or achievements to be materially different from the results, performance or other expectations implied by these forward-looking statements. Forward-looking statements can sometimes be identified by terminology such as "may," "will," "should," "intend," "expect," "believe," "potential," "possible," or their negatives or comparable terminology, as well as other words and expressions referencing future events, conditions, or circumstances. In any forward-looking statement in which the Company expresses an expectation or belief as to future results, there can be no assurance that the statement or expectation or belief will be achieved. Various factors may cause differences between the Companys expectations and actual results, including, among others: the Companys limited operating history; uncertainties inherent in the execution, cost and completion of preclinical studies and clinical trials; risks related to regulatory review and approval and commercial development; risks associated with intellectual property protection; and risks related to matters that could affect the Companys future financial results, including the commercial potential, sales, and pricing of the Companys products. Except as required by law, the Company undertakes no obligation to update the forward-looking statements or any of the information in this release, or provide additional information, and expressly disclaims any and all liability and makes no representations or warranties in connection herewith or with respect to any omissions herefrom.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220707005531/en/

Contacts

Media: Katelyn JoyceCorporate Communications LeadT: 1 877 TEVOGEN, Ext 709Katelyn.joyce@tevogen.com

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Tevogen Bio Appoints Acclaimed Oncologist and Immunotherapy Expert Neal Flomenberg, M.D. as Chief Scientific Officer and Global Head of R&D - Yahoo...

Amendment added to Pennsylvania budget bill would make Pitt, other universities stop fetal tissue research

An amendment just added to the state budget bill would make the University of Pittsburgh promise that they would stop fetal tissue research.

Some politicians and doctors are differing on the topic.

On the heels of Roe v. Wade being overturned, State Representative Jerry Knowles is calling for several universities to stop doing fetal cell research.

Pitt is one of those universities, plus Temple, Lincoln and Penn State.

Pitt is expected to receive $155 million in the next year from grant money, and is known for their fetal cell research and work.

Rep. Knowles told Channel 11, I respect doctors. I dont claim to be a doctor, or a scientist. I dont think you need to be a doctor or a scientist to determine what is unethical, what is evil, and what is barbaric.

Its something local infectious disease physician Dr. Amesh Adalja disagrees with.

We have already seen benefits from stem cell research, and research that derives from fetus cells. Even some of the covid vaccines were developed. This is a life saving technology.

Pitt spokesperson Chuck Finder sent us a statement:

The University of Pittsburgh devotes every dollar of the general support appropriation it receives from the state to help support a tuition discount for Pennsylvania students and families. Were optimistic the legislature will preserve this investment in our students.

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Amendment added to PA budget bill would make Pitt, other universities stop fetal tissue research - WPXI Pittsburgh

Unlike diarrhea in horses, free fecal water (FFW) syndrome is not life-threatening and involves free water being passed before, after, or with normal fecal balls. But because horses bodies need to conserve water, losing excess fluid in their manureeven if it is apparently benignindicates a gastrointestinal (GI) disturbance is making it difficult for the horse to manage or resorb water.

Horses move monumental volumes of water through their gastrointestinal tracts on a daily basis, said Burt Staniar, PhD, associate professor of equine science in Pennsylvania State College of Agricultural Sciences Department of Animal Science, during his virtual presentation at the 2022 EquiSUMMIT.

In terms of intake, horses need approximately 30 liters (1 liter is a bit more than 1/4 gallon) of water a day. A surprising amount of this can come from forage. Staniar said an average 500-kilogram (1,100-pound) horse consuming fresh forage from pasture containing 80% water might take in more than 22 liters of water daily.

This is simply from the forage. Even hay has 10-15% water, said Staniar.

An average horses GI tract contains an estimated 73 liters of water at any given point, which moves continuously between the circulatory and GI systems. For example, the horse secretes about 40 liters of water in saliva per day, and bile and pancreatic secretions add an additional 55 liters of water per day to the small intestine. In the hindgut (the cecum and large colon, or large intestine), however, water is resorbed, not secreted: 15 liters by the cecum and large colon each and an additional 6 liters by the small colon.

Overall, about 100 liters or 25 gallons of water are secreted into and absorbed from the gastrointestinal tract by a horse at rest, said Staniar. Water movements and conservation during exercise become even more critical due to waters essential roles in maintaining health and athletic performance.

He added, A healthy GI tract is integral for supporting these water movements. It is absolutely critical to have intact tight junctions, which are the protein links that hold the colonic cells together lining the walls of the hindgut.

When those tight junctions break down or do not function correctly, which can happen in response to any type of stress, changes in gut permeability could ensue, which negatively affect the horses ability to absorb water.

While risk factors and causes of FFW syndrome are unclear, stress could be involved. Staniar said study results suggest affected horses are lower in the herds social hierarchy, which could be a source of stress that ultimately alters tight-junction function.

Without knowing the exact cause but appreciating that abnormal water resorption is an underlying contributing factor, Staniar recommended evaluating the type of fiber being offered to horses and other nutrients that might enhance GI function.

Fiber is found in fresh and dry forages, including pelleted feeds.

Recognizing that different types of forage have unique chemical and physical properties, we can use a variety of forages to maximize GI health, he advised.

Consider, for example, the different properties of the various forages: long-stem grass hay, alfalfa, beet pulp, whole oats, soybean hulls, and wheat middlings. These, said Staniar, contain different amounts and types of fiber and moisture and can be used in various combinations to enhance gastric function.

For example, the fiber in beet pulp might be more digestible than the fiber in long-stem grass hay, but the fiber in the hay might cause the horse to chew more than the fiber in the beet pulp, the latter example leading to greater saliva production, Staniar noted. Owners need to be open to trying different types and combinations of fiber.

In addition, he explained that dietary fiber facilitates microbial fermentation in the hindgut, with the byproducts providing energy to the horse and supporting the integrity of the intestinal wall.

This concept supports the idea that pre- and probiotics, as well as butyric acid (which feed those hindgut microorganisms), will help maintain tight junctions and can be used in a multiprong approach to managing FFW, said Staniar.

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Free Fecal Water Syndrome in Horses and What To Do About It The Horse - TheHorse.com

There is no wrong way to do Princeton

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Just a few days before graduating as valedictorian of Princetons Class of 2022, Natalia Orlovsky spoke with PAW about her love for both the sciences and humanities and her hopes for going into academia. As a student she worked in a bioengineering lab, served on the peer review board of thePrinceton Undergraduate Research Journal, was an undergraduate course assistant, served on the board of Theatre Intime, and has been involved with the Gender and Sexuality Resource Center. Her advice to future students is to shrug off the feeling that theres a prescribed arc to their experience, so they can feel like theyre doing Princeton correctly, regardless of how theyre doing Princeton.

TRANSCRIPT:

Carlett Spike:From an early age, Natalia Orlovsky has had a love for both the sciences and humanities. In 2018, while a senior in high school, she was featured in aWashington Postarticle about these two varying interests as she was debating whether to attend Princeton to study science or Oxford to study history. While today Natalia is just a few days shy of graduating from Princeton as the valedictorian for the Class of 2022, she ultimately picked the University because it offered a bit of both. She could study science and explore the humanities through her extracurriculars.

Natalia is a molecular biology concentrator from Chadds Ford, Pennsylvania, and pursuing a certificate in quantitative and computational biology. She has earned 10 A-plus grades in six different departments while at Princeton. Heres a few of things shes done on campus: Natalia has worked in the bioengineering lab of Cliff Brangwynne, served on the peer review board of thePrinceton Undergraduate Research Journal, was an undergraduate course assistant for both Organic Chemistry and Introduction to Data Science, served on the board of Theatre Intime, and has been involved with the Gender and Sexuality Resource Center. Her thesis work studies how two different proteins help determine the physical properties, or squishiness, of the cell nucleus, which in turn influences how easily cells can crawl through narrow passageways.

Im Carlett Spike, PAWs associate editor, and Im here today with Natalia to reflect on her Princeton journey, the lessons shes learned, and her plans for the future.

Welcome, Natalia, and thank you for coming on the PAWcast.

Natalia Orlovsky:Thank you for having me.

CS:Its a pleasure. Congratulations again on this huge accomplishment.

NO:Thank you.

CS:Can you tell us how you first found out and your reaction to the news?

NO:Oh man. So, I got an email from Jill Dolan, cryptically informing me that I should get on a Zoom call with her, and I think I, initially in response was like, Oh man, youre kidding! And she was like, No, Im not. (laughter) And I was like, OK, I see! But, I dont know; its been really overwhelming, and I feel super lucky.

CS:When she reached out, did you know the news was coming, or...

NO:Yeah, so I had a bit of forewarning. (laughs)

CS:OK, nice. So we know why you chose Princeton, for the bit of both worlds, but can you reflect on your journey up until this point and how you were able to take classes in both the sciences and humanities?

NO:Yeah, for sure. I think the main thing that drew me to Princeton was that I could do original research as an undergraduate in particular in the sciences, and so I think Ive spent a lot of time doing my independent work and doing research. Before, I started doing my formal independent work and thats been my primary mode of engagement with science, and then for a lot of my elective coursework, Ive leaned more towards English and theater, and then also Ive been really involved in the student theater community on campus, which have been my main routes of entry to the arts sphere.

CS:Can you talk a little bit more about being involved in the arts while focusing on science and finding time for both, and how you find the balance with it all?

NO:Yeah, for sure. Its interesting because I think there is this sense that most art students focus on the arts in their academic coursework as well, so I guess it is somewhat less common to have STEM folks in performing arts, but there are a lot of people who are. And its actually quite cool because its such a different mode of exploration, so its like in the lab youre doing one type of hands-on work and then in the classroom youre doing potentially computational work or youre doing more formal studying, test-taking, etc., and then in a theater context youre on your feet and youre thinking on a completely different axis, and so its kind of nice because then your hobby is legitimately relaxing, (laughs) so its I think it provides a kind of built-in break, so it becomes quite manageable.

CS:Nice. So youve taken a ton of classes at this point. What have been some of your favorites?

NO:Oh, man. So I took a few classes with Professor Bob Sandberg in the English department, which were really, really great. I think they changed how I think about theater a lot and how I think about how storytelling works and what it does for people. I think I I also took a philosophy class called Death,(laughs) which was really interesting. I was taking that during the start of the pandemic, which made for a bizarre relevance (laughs) that I didnt anticipate beforehand, but it, I think, shaped some of my more existential positions at this point.

And then, I think, the other one that I would say is Ive taken a couple of quantitative biology classes that have been super important to me, so one of them is Professor Corina Tarnitas class in the EEB department, and then another one is Ned Wingreens graduate seminar in quantitative biology, and I think I mean, I like math, and Ive liked math for a long time, but I think I didnt really see the overlap between that interest and my very experimental approach to life sciences that I generally take, and so its been really cool to learn about how to apply quantitative tools to answer questions that you cant really answer by experimental means, like questions about how things evolved, for instance, which theres not really a different angle that you can take, and its really cool to see that even with my, I think, comparatively more limited math background, there are lots of cool quantitative avenues towards science that I can take.

CS:Nice. So, you mentioned the pandemic. I was going to ask you about that. Obviously, its been a major part of your college journey. Can you talk about how the pandemic has impacted you personally, and if theres ways that its shifted your perspective and outlook on maybe both what it means to be a student and your career moving forward?

NO:Yeah. I mean, I think a couple of things, but then the first thing is that I think every Princeton student had a different pandemic Princeton experience, and I was really lucky in that I went home to a safe learning environment. And I know that wasnt true for a lot of students, so I think thats worth acknowledging. So I think personally, it was obviously very disappointing to not be able to interact with people and to not be able to do hands-on research for a long time and especially to not be able to do in-person theater performances because Zoom theater really doesnt cut it for me. (laughs)

But I think, all in all, I was really lucky. But I think, more broadly, its I think people have been talking a lot more about what kind of public relationships to science are, so Ive been thinking more about issues of science communication and how I want that to be a part of my future career in science education because I think its increasingly apparent that there is a need to speak responsibly about science and to educate people about science so that the world as a whole can respond to global challenges in an appropriate way.

CS:Following that line of thinking, ultimately, what would you say would be your dream job then?

NO:Oh, man. I think so, tentatively speaking, I think I would like to go into academia because I like both research and teaching a lot, and I want both of those things to be part of my life in some capacity, and even if I dont go into academia, I think informally, at least, I want both mentorship and research to be part of my future career. But thats all Ive got worked out at this stage.

CS:Its totally fine. Theres still tons of time to decide and figure out what you want to do. Switching gears a little bit to the upcoming Commencement, have you given your thought some your speech some thought? Have you written it? Its OK if you havent.

NO:Yeah. Im taking the time-honored Princeton approach of writing it at the last minute, I think.

CS:Are there any themes or messages that youve you really hope to impart on your classmates and how you want to leave them with?

NO:This is very tentative. It might not make it in, but I think some of what Im thinking about right now is that, I think, its an interesting moment to be thinking about transition and to be celebrating transition because I think theres a lot of things that are happening in the world that are really terrible for a lot of people, and things for a long time have been unpleasant for pandemic reasons and social inequality reasons and global turmoil reasons, and so I think that kind of changes the valence of what I think a graduation experience feels like in the moment. And so, I want to be cognizant of that, and I want to acknowledge that, but I dont quite know how yet.

And I think the other thing is that, I think if I could impart anything, I think it would be some kind of wish that people take care of themselves and each other, and I havent thought of a great articulation for that yet, but thats where Im thinking.

CS:Those are good messages.

NO:Thank you.

CS:I wanted to also ask you about your thesis. Can you talk about where the idea came from, and what its been like working on it for a while now?

NO:Yeah, for sure. In my thesis, Im looking at how these two proteins contribute to how squishy the nucleus is, the idea being that the squishier the cell nucleus, the better the cell is at climbing through little spaces and maybe at metastasizing, if its in a cancer context. And, so Cliffs lab generally works on these physical approaches to biology, and so this is, I think, not one of the main focuses of the lab at this point, but that kind of mechanical thinking is very much a part of how he approaches biology, and so I think thats where a lot of it comes from. And for me personally, I think theres just a lot of appeal in being able to take a tiny, microscopic thing and then poke it and see how it changes shape. And Im a massive microscopy nerd, so its been a lot of fun to both learn the relevant techniques to actually do the experiments and to conceptualize the project as a whole.

CS:Nice. So reflecting on the entirety of your journey as a Princeton student, what has been some of the most challenging parts?

NO:For me definitely managing mental health has been a challenge. I think even more so because of the pandemic because youre automatically also isolated from other students and from University resources. So I think a lot of it for me has been learning to manage anxiety and patterns of thinking under intense stress, because I think the Princeton semester is really fast, often painfully so.

And then I think also learning to juggle academic rigor and social health. I think especially during my first two years at Princeton, I was very much locked in a library until two in the morning, that kind of thing, and then I think the pandemic shifted a lot for me in terms of what I prioritize because I think now I spend more time with friends and I try to seek out the people I care about and make sure that theyre doing OK and in the process make sure that Im doing OK, which sometimes it feels like thats not what Princeton is built for. It feels a little bit like the expectation is that school is the first thing that you do and maybe also the last thing that you do, and if youre able to squeeze in a little bit of socializing, then good on you, but I think Ive struggled with that a bit, but Ive come to a better balance now.

CS:Thats good. You mentioned social life. What do you do outside of academics, and what do you do for fun?

NO:I play a lot of board games lately. Thats been whats been happening.

CS:Are you on the Wordle trend?

NO:I am. My friends and I all do it together, which I think is an exceptionally nerdy thing. My partners really into board games, so is our broader friend group, so thats become my go-to social activity.

CS:Favorite board game?

NO:Race for the Galaxy. Its a sci-fi themed card game, essentially.

CS:Awesome. So, you reflected on your own journey, but Im curious what advice you would offer to the incoming class if you could talk to them and just share some tidbits and tips from your journey.

NO:Sure. I think my main thought is that there is no wrong way to do Princeton. I think you come in with the sense that theres this particular arc that is prescribed and that it culminates in thesis work, and thesis work must be massively rewarding in order for you have done Princeton correctly, and the priority has to be this but then you also have to be in 70 million extracurriculars, and I think that thats ridiculous and most people dont actually live like that. I think I dont know anyone who actually lives like that. But coming to that conclusion is hard and is a process, and I think everyone goes through that process. And so I just I hope that incoming students can increasingly feel like theyre doing Princeton correctly, regardless of how theyre doing Princeton.

And also I think I would tell people that this place is hard, and it is OK to be finding it hard, and it is OK to be finding it hard in terms of academics and in terms of social things and in terms of extracurricular things because I think everyone struggles with different stuff.

CS:Absolutely. Great advice. You talked about your dream job. We wont hold it in stone. Its OK if you change your mind, but can you talk about what we can expect to see from you next; what are your plans after Princeton, after graduation; and if you have any other goals youd like to share?

NO:Yeah, sure. So, Im starting a Ph.D. program in the fall, because clearly I didnt get enough of school yet, but yes, Im starting a biological and biomedical sciences program at Harvard, and Im really excited to get to do research full time. I think Ive been pretending to be a grad student for a while, and Ive generally really enjoyed that mode of existence, so I think Im excited to keep doing basic biology research and then really excited to keep growing as an educator in particular, so, those are after taking the summer off because I think a break would be nice.

CS:Are you planning to do anything fun with your break?

NO:Yeah, Im planning to do nothing for much of it, which I think

CS:That sounds lovely.

NO: is a top priority right now, but spending time with family mainly.

CS:Absolutely. Great. Well, Natalia, its been wonderful speaking with you and getting to know you. Thanks again for coming on the PAWcast and best of luck.

NO:Yeah, thank you so much.

PAWcast is a monthly interview podcast produced by the Princeton Alumni Weekly. If you enjoyed this episode, please subscribe. You can find us on Apple Podcasts, Google Podcasts, Spotify, and SoundCloud. You can read transcripts of every episode on our website,paw.princeton.edu. Music for this podcast is licensed from Universal Production Music.

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PAWcast: Valedictorian Natalia Orlovsky '22 on Research, Mental Health, and Pandemic Princeton - Princeton Alumni Weekly

After an initial draft majority opinion overturning Roe v. Wade was leaked, millions of Americans experienced stages of grief and fear. While the implications of overruling Roe v. Wade are frightening, the anti-abortion movements initiatives are not just limited to the control of peoples bodies. Anti-abortion sentiment has become an active way to disenfranchise communities with less money. This political method has even reached the University of Pittsburgh. Pro-life sentiment among PA state House representatives has the potential to end in-state tuition discounts for thousands of students at Pitt.

Representatives advocating for voucher programs have scrutinized the University of Pittsburghs funding for years, but concerns are mounting as Pittsburghs multi-million dollar appropriation from the state is under attack from House Republicans. One of the main factors driving GOP hostility is the concern that Pitt researchers are using fetal tissue for scientific research. This discourse has the potential to end tuition breaks for in-state students, excluding many students from achieving a secondary education.

As the attack on Roe v. Wade has become the forefront of the GOPs party ticket, the University has received criticism locally and nationwide from Republican representatives. Many anti-abortion acitivsts accused Pitt of participating in illegal activities regarding the use of fetal tissue in medical research.

The use of fetal tissue in medical research dates back to the 1930s. Fetal tissue is essential for medical research because as of now, there are no alternatives that provide the same accuracy in research. By law, all fetal tissue donations are voluntary. Informed consent is required for fetal tissue to be collected and provided to researchers. Pitt is not the only school that uses fetal tissue many of the nations leading medical universities use fetal tissue for research. Despite these facts, the University received heavy backlash from GOP representatives and pro-life advocates.

In 2021, Republican state representative Kathy Rapp requested an auditorial general review of the Universitys state and federal funding. This request was a way for representatives to monitor Pitts research practices through a series of public hearings featuring university staff members and professors.

If these allegations are true that scientists at the University of Pittsburgh were harvesting kidneys of unborn babies while their hearts were still beating, they should not only have their taxpayer funding immediately suspended, everyone involved should face criminal charges, tweeted Sean Parnell, another Pennsylvanian Republican representative.

Despite these claims, an outside investigation found that the school was fully compliant with federal and state regulatory requirements regarding its use of fetal tissue.

As we have stated in the past: Fetal tissue research plays a critical role in advancing life-saving discoveries. We remain committed to maintaining robust internal controls and to extending our record of compliance at the state and federal levels, and we take these responsibilities seriously, a Pitt spokesperson told the University Times.

Despite these statements, right-wing media became fixated on the University. David Daleidan, an anti-abortion journalist, likened the National Institute of Healths funding of Pitt programs as an episode of American Horror Story. Fox News covered a 2020 study where scientists altered rodents immune systems with fetal tissue and stem cells to further study skin infections in people. The right-wing media outlet described it as an experiment involving grafting fetal scalps, containing full-thickness human skin, onto rodents. There was even a blog post claiming that Pitt had an illegal Quid-Pro-Quo arrangement with Planned Parenthood of Western Pennsylvania clinics to obtain specimens.

These accusations may seem comical, but they have real-world implications on all Pitt students. On June 30, Pennsylvania lawmakers will determine the 2022-23 budget and ultimately their support for the University of Pittsburghs state funding. Republican lawmakers are adamant that the state shouldnt fund Pitt due to fetal tissue research.

As of June 3, Republican congressmen once again have requested an audit into Pitts fetal tissue research. This time, representatives have directed their attack on UPMCs role in Pitts research, as they believe the prior assessment stopped short. These audits could potentially sway representatives support for Pitts appropriation bill.

If Pitts general appropriation bill is not passed, numerous students will no longer be able to afford the Universitys tuition. In the fiscal year 2020-21, Pitt provided Pennsylvanian students $284 million in tuition discounts. The states appropriation accounted for around 60 percent of that discount.

This funding supports a significant tuition discount for Pennsylvanians that saves each Pitt student about $60,000 over the course of their undergraduate career, said David Brown, Pitts new vice chancellor for government relations and advocacy, to the University Times. Unfortunately, this year more than ever, Pennsylvanias students and families are facing a very real risk of losing their tuition discount.

This tuition discount is a life-changing benefit for many Pennsylvanian families and students. In many cases, it is the only factor that makes Pitt affordable. The fact the bill is at risk due to anti-abortion sentiment among state representatives is an indication of how backward the pro-life movement has become.

When the draft opinion in the case of Dobbs v. Jackson Womens Health Organization was leaked, there was an immediate outcry that the decision to overturn Roe v. Wade would affect poor women the most. As the debate around Pitts funding grows, we are witnessing how the anti-abortion movement not only disenfranchises the bodies of low-income women but also disenfranchises all low-income Americans. By cutting Pitts funding under the cover of the pro-life argument, state representatives exclude thousands of students with low-income backgrounds from higher education and ensure that college no longer functions as the great equalizer.

The issue of Pitts funding shows the disconnect between the life-embracing rhetoric surrounding anti abortion and the cold indifference toward the fate of thousands of students. What were left facing is a group of conservative representatives ready to cut university funding in the name of protecting the unborn, even if that means altering the lives of the living, breathing, students who depend on that money for their futures.

Ebonee Rice-Nguyen writes primarily about political, social and cultural issues. Write to her at [emailprotected].

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Opinion | Pro-Life Representatives may be the reason thousands of students cant afford Pitt - The Pitt News

The repair of old, damaged, or diseased tissues using gene or cell therapies promises a future where people live longer, healthier lives and Ireland is well placed to become a manufacturing hub for products based on this technology.

Gene therapy is the technology used to correct a gene defect that is causing an inherited genetic disease. Cell therapy is the use of living cells from the patient or a donor, to repair tissue or treat an inflammatory condition or disease. These therapies can be used alone or combined for greater effect.

Weve been interested, for a very long time in the development of new treatments for patients involving cell and gene therapy, says professor of cellular therapy at NUI Galway Frank Barry a co-founder of the Regenerative Medicine Institute (Remedi) in 2004.

Over the last several decades there have been some extraordinary, transformative developments in medicine; for example, antibiotics and monoclonal antibodies and these have had a dramatic impact on how diseases were treated, says Barry. Many people believe that cell and gene therapy represent the next transformative innovation that will change medicine.

There are many examples of outstanding success stories, where diseases which were previously untreatable are now actually being treated and were very anxious to continue to play a role in this, says Barry.

The combination of cell and gene therapy has been successful in treating cancers that were thought incurable. For example, stem cells have been taken from the blood of patients with specific cancers, genetically modified so they target a particular cancer, and are delivered back into the patients blood.

Gene therapy has had a troubled history with some adverse outcomes reported from early clinical trials two decades ago. Most notably, and tragically, was the case of 18-year-old Jesse Gelsinger, who died in 1999 during a University of Pennsylvania run gene therapy trial. Jesse suffered from a genetic disease affecting his liver which meant that he was unable to metabolise ammonia.

The learnings from that have proven to be very helpful not to diminish the impact of his death on his family and the tragedy of that, says Prof Tim OBrien, head of medicine at NUI Galway, an Irish pioneer of this field.

In Ireland, the origins of cell and gene therapy research go back to 2004, when Remedi was set up with funding from Science Foundation Ireland (SFI). Then in 2014, the Centre for Cell Manufacturing in Ireland (CCMI) was established. Barry and OBrien have been the key figures driving the process.

From the beginning, the dream of Barry and OBrien was to convert promising gene and cell therapy research into new therapies that could then be tested in clinical trials. Galway was a good place to do it, as it was known as a leading hub for medical device research and manufacturing, and it had the laboratories, hospital tissue facilities and clinical trial expertise that would be required.

Almost two decades down the road, the next step, they say, requires putting in place a national plan for developing a cell and gene therapy industry across the island similar to what has been achieved for medical devices and other high areas dependent on advanced technology, like ICT and pharmaceuticals. The UK offers a model of what can be achieved as it benefits from a decision by government to heavily invest in gene and cell therapy 15 years ago through an independent body it established called the Cell and Gene Therapy Catapult.

The opportunity for gene and cell therapy to grow here in coming years helped attract Dr Meadhbh Brennan, a post-doctoral researcher at Harvard University, back to Ireland. She also worked at the National Institute of Health and Inserm in France before returning to NUIG to set up her own research group.

In France, Brennan had worked on a clinical trial using stem cells to treat bone defects, while in the US her research focused on factors secreted by stem cells which could be used as a therapeutic. While in the US, she was awarded funding from SFI and that provided impetus for her move home, to take up a position at NUIG working at the interface between engineering and medicine.

She has a European Research Council starting grant award to investigate ways of regenerating bone defects, building on her work in this area. There are more than one million bone grafting procedures performed annually in Europe, and after blood, bone is the most transplanted tissue. There are issues with these procedures, however, as bone tissue is limited in quantity and quality and there is often pain at the surgical site for patients.

Brennan and her team are seeking alternatives to bone grafting through the use of byproducts from the manufacturing of stem cells called extracellular vesicles (EVs). These EVs are tiny biological packages that each contain a therapeutic cargo that has been shown to be capable of enhancing healing processes in tissues by delivering healing messages from cell to cell.

Up to now, EVs have been disposed of as waste products from commercial stem cell manufacturing. We want to divert these discarded products and harness their therapeutic potential, Brennan says, This will make the whole stem cell manufacturing process more efficient and sustainable.

Remedi scientists have experience running patient cell therapy trials, with a trial to treat arthritis of the knee using patients own cells having finished and its results set to be reported during 2022. We dont have the formal results yet, but every piece of information that weve seen about this kind of effort suggests that there is a positive benefit associated with delivering cells to these arthritic joints, Barry says. The next step would be to conduct a larger, well controlled, multinational trial of the therapy, which could be led in Ireland.

There is a huge need for new therapies to treat bone defects, given that about 10 per cent of all bone fractures wont heal if left alone, while bone infection and surgery can leave big voids in bone that need to be healed. This is where new approaches based on EVs can come in, says Brennan. These tiny particles hold huge promise for regenerating not only bone tissue, but also older tissues and organs, and have healing potential in other diseases too.

A key challenge to sort out with EV-based therapies is to find a way to safely transport them from the stem cell manufacturing facility to the clinic. Brennan and her team are investigating ways to allow the vesicles to be stored for longer durations at room temperature. The ultimate goal is to develop novel EV treatments that are inexpensive and available off the shelf when a patient has an injured or damaged tissue or needs an anti-inflammatory treatment.

The whole idea about these technologies is that they are regenerative, stimulate repair or correct defects which are chronic, Barry notes. If they work then you are saving years and years of care associated with chronic illness. The economics of this make an awful lot of sense, and the investment that is needed is very much worth it in terms of the long term.

This is a huge new industry which is exploding worldwide and will require advanced manufacturing capacity in all corners of the world, Barry points out. There is an opportunity for Ireland to become a major centre of this, and we have the people, expertise, and infrastructure to allow the industry to develop here. We need to move with lightning speed to capture the opportunity.

The idea of Ireland becoming a global hub for cell and gene therapy and manufacturing is something we should talk about seriously, he adds.

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Tackling chronic disease with gene and cell therapies - The Irish Times

The immune system remembers. Often this memory, primed by past encounters with threats like bacteria or viruses, is an asset. But when that memory is sparked by internal drivers, like chronic inflammation, it can prove detrimental, perpetuating a misguided immune response.

In a new paper in Cell, researchers from the School of Dental Medicine, together with an international team including colleagues at the Technical University of Dresden, lay out the mechanism by which innate immune memory can cause one type of inflammatory conditionin this example, gum diseaseto increase susceptibility to anotherhere, arthritisthrough alterations to immune cell precursors in the bone marrow. In a mouse model, the team demonstrated that recipients of a bone marrow transplant were predisposed to more severe arthritis if their donor had inflammatory gum disease.

Although we use periodontitis and arthritis as our model, our findings go above and beyond these examples, says George Hajishengallis, a professor in Penn Dental Medicine and a corresponding author on the work. This is in fact a central mechanism, a unifying principle underlying the association between a variety of comorbidities.

The researchers note that this mechanism may also prompt a reconsideration of how bone marrow donors are selected, as donors with certain types of immune memory caused by underlying inflammatory conditions might put bone marrow transplant recipients at a higher risk of inflammatory disorders.

In previous work, Hajishengallis had partnered with co-corresponding author Triantafyllos Chavakis of Technical University of Dresden and collaborators to explore the role of innate immune memory. Their findings showed that, just like the adaptive immune systems T cells and B cells, the innate immune systems myeloid cells, such as neutrophils and macrophages, could remember past encounters, becoming more responsive when exposed to a new threat. The work also pinpointed how this memory was encoded, tracing it to the bone marrow, and showed that this trained immunity could be transferred from one organism to another through a bone marrow transplant, protecting recipients from cancer through an innate immune response.

While that is good news, Hajishengallis and Chavakis also believed that trained immunity could be detrimental in the right contexts. While attending a meeting on innate immunity in Greece in 2019, the two scientists brainstormed over dinner at an outdoor tavern, jotting down their thoughts on a napkin. They later formalized some of their hypotheses about this potential dark side of trained immunity in a publication in Nature Reviews Immunology in 2021.

The thoughts went like this: We knew the gum disease periodontitis increased the risk of comorbidities like cardiovascular disease, says Hajishengallis. And the reverse is also true: People with the inflammatory disease colitis, for example, have an increased prevalence of periodontal disease. Different mechanisms have been proposed, but no one unifying mechanism could explain this bidirectionality.

We started thinking about a possible unifying mechanism that could underlie the association between several distinct comorbidities, says Chavakis.

Building on their earlier discovery related to trained precursors in the bone marrow, the scientists set out to see whether they could trace the source of the association between comorbidities to the innate immune training they already knew was happening in the bone marrow.

Setting out to test this hypothesis, the team first showed that, within a week of inducing a mouse to have periodontal disease, the animals myeloid cells and their progenitor cells expanded in the bone marrow. Examining these cells weeks later, after periodontitis was intentionally resolved, the researchers did not notice significant changes in how the cells looked or behaved.

However, these progenitor cells appeared to have memorized the inflammation they were exposed to, as they harbored important epigenetic changes: alterations in molecular markers that affect the ways genes are turned on and off but do not alter the actual DNA sequence. The researchers found that these alterations, triggered by inflammation, could alter the manner in which the genes would be expressed after a future challenge. The overall pattern of epigenetic changes, the researchers noted, was associated with known signatures of the inflammatory response.

Mice with induced periodontal disease also had more severe responses to a later immune system challenge, evidence of trained immunity.

To put the whole picture together regarding the link between inflammatory conditions, the critical experiment, as Hajishengallis explains, was a bone marrow transplant. Mice that had periodontitis, a severe form of gum disease, served as donors, as did a group of healthy mice serving as controls. Two hundred stem cells from their bone marrow were transplanted into mice that had never had gum disease and which had had their own bone marrow irradiated. A few months later, these mice were exposed to collagen antibodies, which trigger arthritis.

Mice that received the transplant from mice with periodontitis developed more severe arthritis than mice that received a donation of stem cells from periodontally healthy mice, says Hajishengallis.

And higher joint inflammation in recipient mice was due to inflammatory cells deriving from the periodontitis-trained stem cells, says Chavakis.

Further experiments suggested that the signaling pathway governed by a receptor for the molecule IL-1 played a vital role in contributing to this inflammatory memory. Mice that lacked IL-1 receptor signaling could not generate the immune memory that made the recipient mice more susceptible to comorbidities, the researchers found.

The work has implications for bone marrow transplants in humans, a common course of therapy in addressing blood cancers.

Of course, its a great thing if you find a matching donor for bone marrow transplantation, says Hajishengallis. But our findings suggest that its important for clinicians to keep in mind how the medical history of the donor is going to affect the health of the recipient.

The work also underscores that blocking IL-1 receptor signaling could be an effective approach to mitigate against these knock-on effects of trained immunity.

Weve seen anti-IL-1 antibodies used in clinical trials for atherosclerosis with excellent results, Hajishengallis says. It could be that it was in part because it was blocking this maladaptive trained immunity.

Follow-up projects are examining how other inflammatory conditions, may be linked with periodontal disease, a sign, the researchers say, of how crucial oral health is to overall health.

Im proud for the field of dentistry that this work, with significance to a wide range of medical conditions, began by investigating oral health, Hajishengallis says.

George Hajishengallis is the Thomas W. Evans Centennial Professor in the Department of Basic and Translational Sciences in the University of Pennsylvania School of Dental Medicine.

In addition to Hajishengallis and Chavakis, coauthors on the study were Penn Dental Medicines Xiaofei Li, Hui Wang, and Gundappa Saha; Xiang Yu of Penns Department of Biology and Shanghai Jiao Tong University; Technical University of Dresdens Lydia Kalafati, Charalampos Ioannidis, and Ioannis Mitroulis; and Mihai G. Netea of Radboud University of Medical Center and the University of Bonn.

The study was supported in part by the National Institutes of Health (grants DE029436 and DE031206) and the Deutsche Forschungsgemeinschaft.

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How one inflammatory disorder exacerbates another | Penn Today - Penn Today