CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Tessera Therapeutics, a biotechnology company pioneering a new approach in genetic medicine known as Gene Writing technology, today announced the expansion of its executive leadership team with appointments of Michael Holmes, Ph.D., Chief Scientific Officer, Iain McFadyen, Ph.D., Chief Data Officer, and Becky Lillie, Chief Human Resources Officer. Jacob Rubens, Ph.D., Co-Founder of Tessera and Senior Principal, Flagship Pioneering, has transitioned from Tesseras Chief Scientific Officer to Chief Innovation Officer. In addition to the three executive appointments, Rebecca Wais, Ph.D., JD, Vice President, Intellectual Property and Legal Affairs, and Ian OReilly, Vice President, Head of GMP Quality, recently joined the Tessera team to bolster the companys internal legal and manufacturing capabilities.

Michael, Iain, and Bec are invaluable additions to our Tessera team and our mission to cure disease by writing in the code of life, said Dr. Geoffrey von Maltzahn, CEO and Co-Founder of Tessera and General Partner, Flagship Pioneering. Their leadership, experiences, and mindsets will be critical in helping to realize our aspirations in genetic medicine, attract and maintain the best talent, and develop our pipeline of Gene Writer candidates to cure and prevent severe diseases.

We set out to revolutionize the field of genetic medicine by pioneering Gene Writing technology that can unlock the therapeutic potential of engineering DNA and address the short-comings of todays gene therapy and gene editing approaches, said Dr. Jacob Rubens. To realize this goal, were building the fields top team across all levels and functions of our organization. Were thrilled that our research will be led by Mike Holmes, whose previous roles included spearheading development of the industrys first gene editing platform and therapeutic candidates.

Michael Holmes, Ph.D., Chief Scientific Officer Dr. Michael Holmes has joined Tessera Therapeutics as its Chief Scientific Officer to lead the development of novel technologies and transformative therapies. Dr. Holmes has more than 20 years of experience working on the development and clinical translation of genome editing- and gene therapy-based approaches. He has an accomplished track record of translating genome engineering technologies to product candidates as evidenced by leading ten therapeutic programs across ex vivo and in vivo therapies. Prior to joining Tessera, Dr. Holmes was the Chief Scientific Officer of Ambys Medicines, and he also held various leadership positions at Sangamo Therapeutics, Inc., including Senior Vice President and Chief Technology Officer.

Dr. Holmes led the efforts that resulted in the first ever clinical candidate of a genome editing-based therapy and has extensive experience in the genome editing of T-cells, hematopoietic stem cells, and hepatocytes. He was also responsible for the research efforts to develop the SB-525 human factor 8 protein (hFVIII) cDNA program, which achieved the highest ever reported level of hFVIII in animal studies and is currently being evaluated in a Phase III study for hemophilia A.

Dr. Holmes holds a Ph.D. in Molecular and Cell Biology from the University of California, Berkeley. He also has a B.S. in Molecular Biology from the University of California, San Diego. To date, Dr. Holmes has authored more than 60 publications in the field of genome editing and gene regulation and he is listed as an inventor on more than 40 issued and pending U.S. patents.

After working in the field of genetic medicine for more than 20 years, I was inspired by the capabilities and performance of Tesseras Gene Writer candidates and their potential to fundamentally reshape the field of genetic medicine, said Dr. Holmes. Our Gene Writer tools can make single base pair changes, insertions and deletions, and write entire genes, each with meaningful advantages over current tools, and without reliance upon viral vectors. I look forward to working with the incredible team to advance our Gene Writing platform and to develop win-state medicines that can transform the lives of patients.

Iain McFadyen, Ph.D., Chief Data Officer Dr. Iain McFadyen serves as Chief Data Officer to help advance Tesseras goal of developing potentially curative medicines across multiple therapeutic areas. Previously, Dr. McFadyen held executive and senior leadership positions at LifeMine Therapeutics and Moderna, Inc., respectively. As Chief Data Officer at LifeMine, Dr. McFadyen oversaw the development of the genomic search-based drug discovery platform, led the growth of the Data Sciences department as well as built a fully integrated informatics platform, and led target identification validation efforts. At Moderna, he founded, built, and led the Computational Sciences department, which included people working in data science, and helped develop the platform that delivered mRNA and lipid nanoparticles to patients in the form of the coronavirus vaccine. Throughout his career, Dr. McFadyen has worked in computational biology, computational chemistry, data science, and machine learning/artificial intelligence. He has experience working across various modalities (including mRNA, proteins, and vaccines) and scientific areas that he will apply to his work at Tessera.

"I was drawn to Tessera because I believe Gene Writing technology is the future of medicine, said Dr. McFadyen. Ive previously developed industrial computational platforms for engineering RNA and for discovering genes with unique functions, and I am thrilled to leverage this experience towards creating and optimizing our Gene Writing platform at Tessera.

Dr. McFadyen earned his Ph.D. in Pharmacology from Loughborough University (UK) and the University of Michigan in the Traynor Lab, later serving as a Postdoctoral Research Associate at the University of Minnesota. He received his B.S. in Medicinal and Pharmaceutical Chemistry from Loughborough University. Dr. McFadyen is the author of 21 publications and the inventor on eight patents and patent families with 16 patent applications pending.

Becky Lillie, Chief Human Resources Officer Becky Lillie joins Tessera as the Chief Human Resources Officer to lead the HR function and oversee talent management strategies and incentives to enable the business strategy. Previously, Ms. Lillie served as the Chief Human Experience Officer at Alexion Pharmaceuticals, Inc., where she modernized HR, IT, and Patient Advocacy departments. As a seasoned human capital strategist with over 25 years of experience in the pharmaceutical industry, Ms. Lillie has deep expertise in designing and executing human-centered organizations, operating models, and corporate governance structures.

In todays quickly evolving and highly competitive biotech industry, its more important than ever to demonstrate strong leadership and to build an employee environment that fosters innovative growth and development, said Ms. Lillie. I look forward to working with Tessera to continue building a robust team of scientists motivated by the challenge of developing a new category of genetic medicines to change how we approach disease.

During her career, Ms. Lille progressed through the ranks at Alexion from Executive Director through to Chief Human Experience Officer over several years, modernizing its HR operation and revamping the R&D operating model in the process. She also held leadership positions in R&D at AstraZeneca and Pfizer Inc. Ms. Lillie earned her B.A. in Communications with an emphasis in Public Relations from the University of North Dakota in Grand Forks.

About Tesseras Gene Writer Tools Tesseras Gene Writer tools are based on natures genome architects, Mobile Genetic Elements (MGEs)the most abundant class of genes across the tree of life, representing approximately half of the human genome. Tessera has evaluated tens of thousands of natural and synthetic MGEs to create Gene Writer candidates with the ability to write therapeutic messages into the human genome. Tesseras research engine further optimizes the discovered Gene Writer candidates for efficiency, specificity, and fidelityessentially compressing eons of evolution into a few months.

About Tessera Therapeutics Tessera Therapeutics is pioneering Gene Writing technology, which consists of multiple technology platforms designed to offer scientists and clinicians the ability to write therapeutic messages into the human genome, thereby curing diseases at their source. The Gene Writing platform allows the correction of single nucleotides, the deletion or insertion of short sequences of DNA, and the writing of entire genes into the genome, offering the potential for a new category of genetic medicines with broad applications both in vivo and ex vivo. Tessera Therapeutics was founded by Flagship Pioneering, a life sciences innovation enterprise that conceives, resources, and develops first-in-category companies to transform human health and sustainability. For more information about Tessera, please visit http://www.tesseratherapeutics.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211208005310/en/

Go here to read the rest:
Tessera Therapeutics Adds New Executives to its Leadership Team as the Company Continues to Pioneer Gene Writing Technology as New Category in Genetic...

Introduction

Despite race being a socio-political system of categorization without a biologic basis, race has historically and continues to play a role in medical teaching and clinical decision making within health care. Race permeates clinical decision making and treatment in multiple ways, including: (1) through providers attitudes and implicit biases, (2) disease stereotyping and clinical nomenclature, and (3) clinical algorithms, tools, and treatment guidelines. While some diseases have higher prevalence among individuals with certain genetic ancestry, genetic ancestry is poorly correlated with commonly used social racial categories. The use of race to inform clinical diagnoses and decision making may reinforce disproven notions of race as a biological construct and contribute to ongoing racial disparities in health and health care. This brief provides an overview of the role of race in clinical care and discusses the implications for health and health care disparities and efforts to advance health equity.

Despite there being no biologic basis to race, the medical and scientific community have used race to explain differences in disease prevalence and outcomes. The Western concept of race arose as a system of hierarchical human categorization to support European colonialization, oppression, and discrimination of non-European groups. Within U.S. medical curricula, the concept of race led to theories of biological inferiority of people of color and White supremacy, which fueled an array of atrocities in medicine including forced sterilization efforts targeting Black and Native American women, the use of Henrietta Lacks cells for scientific research without consent or acknowledgement, and the infamous Tuskegee Syphilis study, among others. Although research has since disproven the existence of universal biologic differences by race, some recent scientific studies continue to suggest that genetic differences between racial groups may explain differences in health outcomes. For example, an article published in 2020 originally suggested that unknown or unmeasured genetic or biological factors may be contributing to increased severity of COVID-19 illness among Black people, although the article was later revised to clarify that the difference is most likely explained by societal factors. Recent research further suggests that measures of demographic characteristics and socioeconomic position may be more effective than genetic characteristics in explaining disparities in cardiovascular disease between Black and White adults.

There have been growing calls against using race as a factor to explain health differences without acknowledging the role of racism. Contemporary science has demonstrated that race is a social category with no basis in biology. Race is a poor proxy for genetic ancestry and large genetic studies have demonstrated more variation within defined racial groups (intra-racially) than there are between different racial groups (inter-racially). Within the medical and scientific community, there have been longstanding critiques of using racial classifications in diagnosis and treatment of disease. Recently, there have been calls for research studies and guidance in the medical community to name and examine the role of racism versus race as a key driver of health inequities to avoid perpetuating disproven understandings of biologic differences by race.

Although race is not tied to biologic differences, understanding differences in health and health care by race and ethnicity remains important for identifying and addressing disparities in health and health care that stem from racism and social and economic inequities. Complete and accurate race and ethnicity data is key for identifying disparities and taking action to address them. However, there are longstanding gaps and limitations in racial and ethnic data within health care. In addition to deficiencies in survey and administrative data, many institutions report gaps in electronic health record (EHR) data on race, with substantial misclassification of self-reported race and preferred language. The largest discrepancies between EHR demographic data and self-reported data are among individuals who identify as Hispanic.

A significant and longstanding body of research suggests that provider and institutional bias and discrimination are drivers of racial disparities in health, contributing to racial differences in diagnosis, prognosis, and treatment decisions. Prior work suggests that providers historically were more likely to perceive individual patient factors rather than provider or health system influences as causes for health disparities. For example, studies have found that providers view Black patients as less cooperative with medical treatment and that providers associate Hispanic patients with noncompliance and risky behavior. A 2015 systematic review of published studies showed that most health care providers appear to have implicit bias in terms of positive attitudes towards White people and negative attitudes towards people of color. While some studies have found no link between bias and provider treatment behaviors, others have demonstrated that provider bias correlates with poorer patient-provider interactions and is associated with disparities in pain management and empathy. Providers who endorse false beliefs about biological differences by race report lower pain for Black patients compared to White patients, which has been linked to systematic undertreatment for pain of Black patients. Similarly, compared to White patients in emergency departments, Hispanic and Asian patients are less likely to receive pain assessments and appropriate pain medication.

Research also shows that patients report being treated unfairly because of their race/ethnicity while accessing health care. For example, a 2020 KFF/the Undefeated survey of adults found that Black and Hispanic adults are more likely than White adults to report they were personally treated unfairly because of their race and ethnicity while getting health care in the past year. Black adults also are more likely than White adults to report negative experiences with health care providers, including feeling a provider did not believe they were telling the truth, being refused a test or treatment they thought they needed, and being refused pain medication. In addition, Black and Hispanic adults are more likely than their White counterparts to say it is difficult to find a doctor who shares their background and experiences and one who treats them with dignity and respect.

Some medical training approaches and materials use imprecise labels conflating race and ancestry, portray diseases through racial stereotypes, and rely on racial heuristics (i.e., mental shortcuts or associations) for teaching clinical diagnosis. Preclinical lectures and clinical vignettes for teaching use nonspecific labels (e.g., Black instead of Nigerian/Haitian and Asian instead of Chinese/Vietnamese/Pakistani) and may misuse race as a surrogate for genetic ancestry. In some cases, they inappropriately use race as a proxy for differences in socioeconomic status, health behaviors (such as diet), or other factors that may influence access to health care or risk of disease. In addition, lecture materials commonly present racial differences in disease burden without historical or social context, which may contribute to students connecting diseases with certain racial groups and ascribing differences to genetic predisposition. For example, preclinical lecturers often teach that recurrent lung infections in White individuals are indicative of cystic fibrosis, which may result in missed diagnoses of cystic fibrosis among Black patients. The hereditary condition glucose-6-phosphate dehydrogenase (G6PD) deficiency, which can cause severe anemia, affects individuals of all racial and ethnic backgrounds, with highest prevalence in Africa, the Middle East, and certain parts of the Mediterranean and Asia. However, lecturers and board materials teach students to have higher clinical suspicion for diagnosis of this deficiency in Black patients. In nearly all medical learning resources, Lyme disease is depicted predominantly on White skin and is often diagnosed much later when the disease has progressed to arthritic stages among Black patients. Other examples of connecting race to disease exist in medical textbooks. For example, Black skin is more commonly used to depict sexually transmitted diseases. A recently recalled textbook for nursing students published in 2017 suggested that there were racial differences in how patients experience and respond to pain. The text described Black patients as reporting higher pain intensity than other cultures, Hispanic patients as having wide expression of pain (some are stoic and some are expressive), Asian patients as valuing stoicism as a response to pain, and Native American patients as being less expressive both verbally and nonverbally. Beyond teaching materials, medical board examinations often test students based on race-based guidelines and heuristics.

Some disease names use racial or geographic terms that link diseases to certain groups or communities. For example, congenital dermal melanocytosis was formerly referred to as Mongolian spot. Similarly, Down syndrome was first described as Mongolism by a 19th century British physician who believed that patients with the genetic disorder resembled individuals of Mongolian descent. As another example, vancomycin infusion reaction was formerly called Red Man syndrome, evoking racist connotations against Indigenous American people. Clinical nomenclature has shifted towards more descriptive language, although in some cases, disease naming is tied to place of discovery. Disease names incorporating geography may still perpetuate racist-xenophobic sentiment. In 2015, the World Health Organization noted associating disease names with geography may result in backlash towards members of particular ethnic communities. This experience was seen in the recent use of the label China virus for the COVID-19 virus, which has been associated with an increase in public anti-Asian sentiment and Asian hate crimes, as well as an increase in depressive symptoms among individuals identifying with multiple Asian subgroups. Moreover, a recent KFF survey of Asian community health center patients found that one in three felt more discrimination based on their racial/ethnic background since the COVID-19 pandemic began in the U.S. and 15% said they had been accused of spreading or causing COVID-19.

While some diseases have higher prevalence among individuals with certain genetic ancestry, the practice of using race within clinical calculators and screening metrics may contribute to health disparities. Today, clinical calculators across multiple specialties assign differential risk for certain diseases or conditions based on race. Prior work has identified a range of examples of clinical calculators that use race (Appendix Table 1). One of the most well-known examples of this practice is within nephrology, where separate measures of kidney function (i.e., estimated glomerular filtration rates, eGFRs) are applied to Black patients compared to non-Black patients. However, similar examples are seen across medicine. For example, a common calculator used to predict success of vaginal birth after Cesarian (VBAC) section had a correction factor for both Black and Hispanic race that decreases the success of VBAC for Black and Hispanic patients by 67% and 68% respectively. This tool may bias providers into disproportionately counseling these patients towards undergoing a Cesarian section. Similarly, pulmonary function tests have a race correction factor, East Asian race is considered a major risk factor for neonatal jaundice, and a different Body Mass Index threshold is used to recommend diabetes testing among asymptomatic Asian and Pacific Islander patients. Given that race is an extremely inconsistent proxy for genetic ancestry, this use of race within clinical calculators may lead to both undertreatment and overtreatment of racialized individuals, and delays in diagnosis and clinical care.

Research shows that some clinical tools may be less effective or misused for certain populations. For example, pulse oximeters have low accuracy in measuring oxygen saturation in darker skin and are three times as likely to miss low oxygen levels in Black patients compared to White patients. Such discrepancies may contribute to delayed intervention and increased mortality for Black patients with COVID-19. In pediatrics, findings suggest that jaundice measurement tools (i.e., bilirubinometer for measurement of transcutaneous bilirubin) have varied reliability based on skin color, with underestimates of risk in lighter skin and overestimates in darker skin tone. Overestimates of bilirubin using transcutaneous measurements may result in unnecessary follow-up blood work (an invasive process for infants), increases in follow-up visits and commute to clinics, and increased infant caregiver distress. In lower resource settings where serum bilirubin measurement is unavailable and transcutaneous bilirubinometry continues to be the primary method for infant monitoring, underestimates of risk may result in delayed intervention for the life-threatening condition neonatal kernicterus, while overestimates of risk for hyperbilirubinemia may result in unnecessary prolonged hospital stays and treatment. In dermatology, the dearth of images depicting lesions on dark skin in medical and dermatologic textbooks and lack of representation of providers with darker skin in the specialty may result in reduced clinician ability to identify life-threatening dermatological presentation on people of color (e.g., sepsis, cellulitis, or severe drug reactions to medications). Skin cancer, while less common in Black and Hispanic patients, is often diagnosed later with subsequently lower survival rates. Fitzpatrick skin type (FS) is the most commonly used skin type classification system in dermatology. It was originally designed to describe the likelihood of skin to burn from UV light exposure but is misused by many providers to describe skin color as a proxy for race.

Preventing against racial bias will be important as use of artificial intelligence and algorithms to guide clinical decision-making continue to expand. The health care system is increasingly using artificial intelligence and algorithms to guide health decisions. Research has shown that these algorithms may have racial bias because the underlying data on which they are trained may be biased and/or may not reflect a diverse population. For example, one study found that an algorithm designed to identify patients with complex health needs resulted in Black patients being assigned the same level of risk as White patients despite being sicker. This unintended bias occurred because of underlying racial bias in how the algorithm was designed, implemented, and interpretedthe algorithm used health care costs to predict health care needs, but Black patients have lower health care costs in part because they face greater barriers to accessing health care. Other examples have found that skewed dermatological datasets result in less accurate models and decreased ability to diagnose skin conditions among darker skin tones. However, research also suggests that carefully designed algorithms can mitigate bias and help to reduce disparities in care.

Race also factors into some medication prescribing decisions, but the use of race is often based on limited evidence from small studies and may result in inappropriate dosing and treatment. In 2005, the U.S. Food and Drug Administrative approved the drug BiDil as a race-specific drug to treat heart failure among African Americans. It was subsequently critiqued for misguided marketing due to using race as a proxy for genotype, which was not evaluated in the study from which conclusions were drawn, although it remains approved as a race-based drug today. There are additional examples of race-based prescribing guidelines. For example, hydrochlorothiazide is recommended as first line hypertension therapy for Black patients based on Joint National Committee (JNC) Hypertension guidelines, as opposed to ACE inhibitor therapy for all other groups due to presumed inefficacy of these agents among Black patients. Eltrombopag, a drug used to treat thrombocytopenia, has a lower recommended starting dose for East Asian patients compared to all other patients. Similarly, the Food and Drug Administration recommends a lower starting dose for Crestor (a statin, used to lower lipid levels) for Asian patients based on a gene that confers metabolic variability, despite the understanding that this gene may be prevalent among any population. There has been ongoing discussion around race-based dosing and the utility of race-based genetic screening for drugs such as warfarin (commonly used for anticoagulation therapy) and abacavir for HIV treatment. Medical community viewpoints on race-based prescribing vary. For example, a study of American cardiologists found that many providers believe race-based drug labels in treatment of heart failure may help prescribe effective medications sooner, while others expressed concerns that considering race could potentially harm patients by resulting in some patients not receiving the drug.

The use of race in the emerging field of pharmacogenomics has come under increasing scrutiny. Pharmacogenomics explores the relationships between genes and drug effects and is viewed as a way to potentially personalize medical therapy. Pharmacogenomics research often uses race to guide decisions about genetic screening prior to using certain drugs to prevent against adverse drug events based on the assumption that certain racial categories may have high or low prevalence of certain genes. Proponents argue that race-based targeting in the field of pharmacogenetics is useful to propel personalized medicine for patient care at the individual level. However, critiques of race-specific therapies express concerns around attempting to address health disparities through commercial drug development versus examining upstream structural factors that may explain differences in treatment response. Moreover, as noted, genetic variation within certain racial/ethnic groups can exceed variation across racial/ethnic categories, suggesting limited utility of this approach and that it may run counter to personalized medicine by treating people based on groupings that have limited genetic association. Current work has limited representation from communities of color, resulting in less extrapolatable, premature recommendations for clinical screening for diverse communities. In addition, inequities across the continuum of drug development and clinical trial participation and evaluation may exacerbate existing disparities in medication access for communities of color, including decreased access to novel, high-cost medications and lower-cost generic therapies.

The use of race within clinical decision making and treatment may reinforce disproven concepts of racial biology and exacerbate health inequities. Race continues to permeate medical teaching and clinical decision making and treatment in multiple ways, including: (1) through providers attitudes and implicit biases, (2) disease stereotyping and nomenclature, and (3) clinical algorithms and treatment guidelines. Racial bias among providers may contribute to poorer quality of care and worse health outcomes. Racial stereotyping of disease and use of race in clinical algorithms and treatment guidelines may lead to errors in clinical diagnosis and management (overtreatment or undertreatment and other delays in clinical care), which may perpetuate and potentially worsen health disparities. Moreover, continued use of race as a biological concept limits examination and understanding of social drivers of health inequities, including racism, and contributes to ongoing racial bias and discrimination among providers.

There have been growing efforts within the medical community to re-evaluate and revise practices around the use of race within clinical care and efforts to move towards race-conscious (as opposed to race-based) medicine. In 2020, the American Medical Association (AMA) adopted new policies to recognize race as a social construct and, as part of these policies, encourages medical education programs to recognize the harmful effects of using race as a proxy for biology in medical education through curriculum changes that explain how racism results in health disparities. In September 2020, the House Ways and Means Committee announced a Request for Information around the misuse of race in clinical care. The Agency for Healthcare Research and Quality (AHRQ) similarly announced in March 2021 a Request for Information on the use of clinical algorithms that have the potential to introduce racial/ethnic bias into healthcare delivery. A subsequent Ways and Means final report released in October 2021 found that professional societies suggest more research (with evaluation of unintended consequences of removing race correctors) is needed before decisions can be made, as a growing number of institutions have removed race from clinical calculators. For example, in the past year-and-a-half, Mass General Brigham hospital, the University of Washington, Vanderbilt University, and NYC Health and Hospitals have all removed race corrections from kidney function estimates. The UC Davis School of Medicine also eliminated race-based reference ranges from renal function estimates, followed shortly by UCSFs release of a new approach to estimate kidney function without race. Moreover, both the American Society of Nephrology and National Kidney Foundation have outlined approaches to diagnose kidney disease without race. In November 2021, the New York City Department of Health launched a Coalition to End Racism in Clinical Algorithms, pledging to end race adjustment in at least one clinical algorithm and to create plans for evaluation of racial inequities and patient engagement. Additionally, some commonly used medical calculators have made use of race correction factors optional, while others have removed them entirely (see Appendix Table 1). In contrast, other institutions have held off on making changes to clinical calculators or guidelines, noting potential downstream implications for other aspects of clinical care and management.

Looking ahead, continued education of health care providers and students to eliminate beliefs of biologic differences by race, improving pedagogy around distinctions between race and genetic ancestry, and reducing racial bias and discrimination will be important, as will efforts to increase the diversity of our health care workforce. Moreover, continued careful evaluation of how race factors into clinical decision-making through clinical guidelines, tools, and algorithms will be important for mitigating biased decision making, particularly as the use of artificial intelligence and machine-driven algorithms to guide clinical decisions expand.

Michelle Tong is a fourth year medical student at the University of California, San Francisco, completing a health policy fellowship with the Kaiser Family Foundation. Samantha Artiga serves as Vice President and Director of the Racial Equity and Health Policy Program at KFF. The authors thank Dr. Louis H. Hart III and Dr. Monica Hahn for their expertise and subject matter review. Dr. Louis Hart is the Medical Director of Health Equity for Yale New Haven Health System and Assistant Professor of Pediatric Hospital Medicine at the Yale School of Medicine. Dr. Monica Hahn is the Co-Founder of the Institute for Healing and Justice in Medicine and Associate Clinical Professor at UCSF in the Department of Family and Community Medicine.

Go here to read the rest:
Use of Race in Clinical Diagnosis and Decision Making: Overview and Implications - Kaiser Family Foundation

The consortium brings together genome-wide association data from 200 cohort studies across the globe, allowing research teams to closely investigate key genetic variation related to blood cholesterol levels in a lot of people at once. U.S. veterans participating in the Million Veteran Program were a major contributor to the increased diversity of the GLGC. In all, around 500 scientists who have collected and analyzed these data are credited as co-authors.

The researchers already knew they needed many, many participants in order to draw big conclusions about lipid levels. What they didnt know in advance was exactly how big the benefit would be of studying diverse samples.

Of three aspects of the research they examined, diversity made a big difference for two of them, and a smaller difference for the third. Willer said they identified approximately the same number of total genetic variation related to lipids (thousands of them), irrespective of the level of diversity.

However, for homing in on the functional gene, or for predicting high cholesterol levels, researchers report that diversity was critically important.

We find that increasing the diversity of the populations studied rather than simply increasing sample size more efficiently identifies the genetic variants that control cholesterol levels in our blood, Assimes said. Importantly, we can potentially level the playing field when it comes to predicting cholesterol levels if we introduce diversity into our study design, and the more diversity we introduce, the better.

LDL cholesterol is a warning bell for future cardiovascular events like heart attacks, so a high cholesterol level in an annual physical is likely to lead to a discussion about how to lower it.

If you could find out in advance that you were more susceptible to having high blood lipids, or high risk of heart attacks, then you could reduce your cholesterol before it even becomes a problem, Graham said.

SEE ALSO: Cholesterol-carrying protein found to help suppress immune response in pancreatic tumor microenvironment

We hope this study will one day allow physicians to better identify people at risk of high cholesterol and cardiovascular disease who may benefit from lifestyle changes or lipid-lowering medication earlier in life, she added.

This study also suggests that genetic studies of any diseases would likely benefit from studying people of diverse ancestries, researchers said.

We should work hard to ensure that genetics research benefits all people, and improving diversity of ancestries represented in research is an important step towards equality, Willer said.

Paper cited: The power of genetic diversity in genome-wide association studies of lipids, Nature. DOI: 10.1038/d41586-021-02998-2

The rest is here:
Making the case for more diversity in genetic research - Michigan Medicine

Carlos Fernndez-Hernando

Carlos Fernndez-Hernando, whose work combines cell biology, genetics, and mouse models to study lipid metabolism and cardiovascular related disorders, was recently appointed the Anthony N. Brady Professor of Comparative Medicine and Pathology.

He is also a member of the Vascular Biology & Therapeutics Program and the Yale Center for Molecular Metabolism.

After earning a bachelors degree in chemistry and his Ph.D. in biochemistry/molecular biology from Universidad Autnoma de Madrid in Spain, Fernndez-Hernando completed a postdoctoral fellowship at Hospital Ramn y Cajal, Spain. He then continued his postdoctoral training with Prof. William Sessa at Yale from 2005 to 2009. Then, after starting his laboratory in the Department of Medicine at New York University, he returned to Yale in 2013.

His research aims to identify and characterize novel mechanisms by which cholesterol and lipoprotein metabolism is regulated. Work from his group identified miRNA-33a/b, an intronic miRNA encoded within the intronic sequences of SREBP genes, the master transcriptional regulators that control lipid metabolism. In a number of relevant studies his group was able to demonstrate that miRNA-33a/b provides a critical link between the regulation of cholesterol and fatty acid biosynthesis by SREBP and cholesterol efflux, high-density lipoprotein (HDL) biogenesis and fatty acid oxidation pathways. Fernndez-Hernando group and colleagues found that pharmacological inhibition of miR-33 increases hepatic ABCA1 expression, circulating HDL-C and attenuates the progression of atherosclerosis. His group has also uncovered the first non-coding RNA (miRNA-148a) that regulates plasma low-density lipoprotein (LDL)-C levels via hepatic LDLR using a genome-wide miRNA screen. These findings correlate with recent reports that identified a genetic variation in the miR-148a locus associated with plasma LDL-C and triglycerides in humans. Together, these contributions have provided novel insights about the molecular mechanisms that regulate cellular lipid homeostasis and lipoprotein metabolism.

Fernndez-Hernando has authored or co-authored more than 150 research articles, many of them in prominent journals, including Science, Nature, Nature Medicine, Cell Metabolism, Journal of Clinical Investigation and Proceding of the National Academy of Sciences, among other publications. He has been the recipient of numerous awards for his contributions in the field of lipid metabolism and vascular biology including the Irvine Page Young Investigator Award (American Heart Association), Springer Award (North American Vascular Biology Association), David L. Williams Award (Kern Lipid Conference), Established Investigator Award (American Heart Association), Jeffrey M. Hoeg Atherosclerosis, Thrombosis & Vascular Biology Award in Basic Science and Clinical Research (American Heart Association), R35EIA from NHBLI and the Folkman Award in Vascular Biology (North American Vascular Biology Association).

Read more here:
Fernndez-Hernando named Anthony N. Brady Professor of Comparative Medicine - Yale News

News Release

Wednesday, December 8, 2021

Researchers have linked a rare genetic mutation found mostly in Black Americans and other people of African descent to an earlier onset of heart failure and a higher risk of hospitalization. The findings suggest that earlier screening for the mutation could lead to faster treatment and improved outcomes for heart failure in this vulnerable group, the researchers said. The results of the study, which was largely supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, appear in the Journal of the American College of Cardiology: Heart Failure.

This is the most comprehensive evaluation of the association between this mutation and measures of cardiac structure, heart function, and heart failure risk in an exclusively Black population, said lead study author Ambarish Pandey, M.D., assistant professor of internal medicine in the Division of Cardiology at University of Texas Southwestern Medical Center in Dallas. The results also highlight the importance of early genetic screening in patients at higher risk for carrying the mutation.

Heart failure is a chronic, debilitating condition that develops when the heart cant pump enough blood to meet the bodys needs. Despite the name, it does not mean that the heart has stopped beating. Common symptoms include shortness of breath during daily activities or trouble breathing when lying down. The condition affects about 6.5 million people in the United States alone. Black Americans are at higher risk for the condition than any other racial/ethnic group in the U.S., and they experience worse outcomes.

The genetic variant studied in the current research had long ago been linked to a higher risk of heart failure in people of African ancestry. Known as TTR V142I, the gene can cause a condition called transthyretin amyloid cardiomyopathy, which is potentially fatal because protein builds up inside the heart. However, little was known about the impact of the mutation on important clinical-related factors such as heart structure, heart function, hospitalization rates, and blood biomarkers.

To learn more, the researchers studied TTR V142I in a group of middle-aged participants from the 20-year-long Jackson Heart Study, the largest and longest investigation of cardiovascular disease in Black Americans. Of the 2,960 participants selected from the study, about 119 (4%) had the genetic mutation, but none had heart failure at the start. The researchers followed the participants for about 12 years between 2005 and 2016.

During the study period, the researchers observed 258 heart failure events. They found that patients who carried the genetic mutation were at significantly higher risk of developing heart failure, compared to those without the mutation. These patients also developed heart failure nearly four years earlier and had a higher number of heart failure hospitalizations. Researchers said they found no significant difference in death rates between the two groups during this study period.

During follow-up studies, however, they observed significant increases in blood levels of troponin, a protein complex that is an important marker of heart damage, among carriers of the genetic mutation. They did not see any significant associations between the genetic mutation and changes in heart structure and function as evaluated by echocardiographic and cardiac MRI assessments.

What that means is that the gene is causing heart damage slowly over time, said Amanda C. Coniglio, M.D., the lead author of the study and a physician with Duke University School of Medicine in Durham, North Carolina. The changes are subtle but significant.

The researchers noted that more studies will be needed to continue assessing participants heart structure and function and to see, long-term, if increased hospitalization risk translates into higher risk of death.

Identification of genetic susceptibility to amyloid cardiomyopathy is an important advance related to heart failure, especially given its disproportionate effect on older and multiethnic populations, said Patrice Desvigne-Nickens, M.D., a medical officer in the Heart Failure and Arrhythmia Branch in NHLBIs Division of Cardiovascular Sciences.

Adolfo Correa, M.D., Ph.D., study co-author and former director of the Jackson Heart Study, agreed. About half of Black American men and women living in the United States today have some form of cardiovascular disease, but the root causes are poorly understood, he said. This study brings us a step closer to better understanding this particular form of gene-related heart failure, as well as the life-saving importance of early screening.The Jackson Heart Study is supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I/HHSN26800001) and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from the NHLBI and the National Institute on Minority Health and Health Disparities. Additional NIH funding support includes the National Institute of Diabetes and Digestive and Kidney Diseases grant 1K08DK099415- 01A1; National Institute of General Medical Sciences grants P20GM104357 and 5U54GM115428.

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit http://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Transthyretin V142I Genetic Variant and Cardiac Remodeling, Injury, and Heart Failure Risk in Black Adults. JACC-Heart Failure.DOI: 10.1016/j.jchf.2021.09.006

###

More:
Rare gene mutation in some Black Americans may allow earlier screening of heart failure - National Institutes of Health