1. < Cardiology/Epi

Last week, I shared an overview of our department’s achievements in securing new federal grant funding during FY 22-23 to support a broad range of research projects, covering multiple areas of health and science. This week it is a pleasure to continue the celebration by highlighting the successes of our colleagues at Veterans Affairs Greater Los Angeles Health Care (VA GLA). The department of medicine (DoM) has 85 faculty at the VA with VA-supported research salary effort. They have been incredibly productive. In addition to over $76,733,528 in total new and existing non VA, grant awards, predominantly from 48 NIH grants, including an NIH Program Project, our VA faculty had a stellar year (FY 22-23) in securing new funding from the US Department of Veterans Affairs (VA) for studies that address the health of our veteran community, with important implications for the broader community.

Under the leadership of DoM Executive Vice Chair, VA Greater Los Angeles Healthcare System, Dr. Zhaoping Li, the VA division portfolio has witnessed tremendous growth in the past year. VA-funded projects include four career development awards that provide five years of physician salary and research support, two Senior Clinician Scientist Investigator (SCSI) Awards providing up to 8 years of research program and salary support, among many other awards. This week, I will highlight the  greater than $30 million in direct cost from 22 new grants and awards from the VA.

I am proud to celebrate our colleagues at the VA, for their exemplary scientific and clinical achievements and salute our junior faculty who earned career development awards (CDAs) and our senior colleagues who received SCSI awards.

VA Career Development Awards

Senior Clinician Scientist Investigator (SCSI) Awards

Congratulations to all our colleagues at the VAGLA! 

As noted last week, new federal grant funds continue to rain on the DoM this new fiscal year and I will spotlight  more members of our community who recently learned that they received federal funding for their research initiatives!

David H. Gonzalez Awarded MOSAIC K99/R00 from the  National Institutes of Environmental Health Sciences (NIEHS) for the study, “Impact of Biomass Burning Aerosol and Humic-like Substances on Iron Homeostasis and Atherosclerosis”.

We begin with David H. Gonzalez, PhD, a postdoctoral fellow in Dr. Jesus Araujo’s Environmental Cardiology & Vascular Biology Lab. Dr. Gonzalez was awarded a K99/R00 MOSAIC project titled “Impact of Biomass Burning Aerosol and Humic-like Substances on Iron Homeostasis and Atherosclerosis.”

Dr. Gonzalez shares that wildfires episodes are on the rise globally driven by climate change and expansion of the wildland-urban interface. Wildfire smoke exposure has been linked to increased cardiovascular morbidity and mortality with disproportionate impacts on vulnerable and underserved populations. This work seeks to fill a surprising gap in knowledge: the cardiovascular risks associated with wildfire smoke inhalation. In this study, he will investigate if woodsmoke particle exposure leads to an iron imbalance in the lungs and if this ultimately leads to cardiovascular effects such as plaque buildup in the arteries (atherosclerosis). Dr. Gonzalez hopes this work can help determine biomarkers associated with cardiovascular risk that may guide emergency medical management and inform policy decisions surrounding wildfire smoke exposure.

“This work proposes an interdisciplinary approach to understand far reaching global health impacts of a growing threat, wildfires. To understand this, we need to bring together the worlds of atmospheric chemistry, exposure science, and toxicology. We hope this work sheds light on wildfire smoke toxicity and serves as a model for future interdisciplinary work critically needed to address the multifaceted issues of air pollution health impacts,”

states Gonzalez.

Dr. Gonzalez will be supported by a career advisory mentoring team, chaired by Dr. Araujo and consisting of distinguished faculty from The David Geffen School of Medicine. This includes Professors: Tomas Ganz, John Belperio, Srinivasa T. Reddy, and Chi-Hong Tseng. Additionally, Dr. Andrew Ghio a medical officer at the U.S. Environmental Protection Agency (EPA), UNC, Chapel Hill will be providing support for this work.

The Maximizing Opportunities for Scientific and Academic Independent Careers (MOSAIC) program was recently launched by the NIH to support a cohort of early career, independent investigators from diverse backgrounds conducting research in NIH mission areas. The long-term goal of this program is to enhance diversity in the biomedical research workforce.

Congratulations David!

Mina Sedrak, MD, MS Awarded R01 to Study How Exercise and Senolytics Affect Physical Function and Markers of Biological Aging in Breast Cancer Survivors

Mina Sedrak, MD, MS an associate professor of medicine, recently recruited to the division of hematology/oncology, has been awarded $3.4 million over five years for his research examining how exercise and senolytics impact accelerated aging due to treatments used for breast cancer. Dr. Sedrak shares that with ever-improving screening strategies and more effective treatments, cancer survivors are now living longer. However, with this step forward, a new problem has emerged: treatments that cure or control cancer accelerate aging. One mechanism that is thought to drive cancer treatment-related accelerated aging is cellular senescence. Cellular senescence is a fundamental aging process characterized by cell cycle arrest. Senescent cells accumulate in aging tissues and secrete pro-inflammatory factors that drive age-related functional decline. We have observed that, in breast cancer survivors, chemotherapy induces the persistent presence of high levels of circulating senescent cells, and that survivors with high senescent cell burden are more likely to experience chemotherapy-induced fatigue, neuropathy, and functional decline. In preclinical models, he showed that senescent cells can be targeted and reduced with interventions such as exercise or senolytics (drugs that selectively ablate senescent cells). In mice, senolytics combined with exercise yielded a greater reduction in senescent cells compared to either intervention alone. However, the ability of exercise and senolytics to reduce senescent cells and, ultimately, improve physical function in breast cancer survivors has not been tested.

In the study, Dr. Sedrak proposes a phase II multicenter, randomized, placebo-controlled trial using a 2x2 factorial design to determine the effects of exercise and senolytics, given in combination or alone, on physical function and markers of biological aging in breast cancer survivors.

“We hypothesize that targeting senescent cells via exercise and senolytics in breast cancer survivors will yield independent and additive effects to prevent chemotherapy-induced accelerated aging,”

said Dr. Sedrak

“As the number of breast cancer survivors rises dramatically (estimated to be >6 million by 2040), mitigating chemotherapy-induced accelerated aging is an urgent public health issue. If our hypothesis is correct, the impact on clinical practice would be substantial and of paramount importance,”

he added.

Arleen Brown, MD, PhD, Alejandra Casillas, MD, MSHS, Soma Wali, MD Awarded National Heart, Lung, Blood Institute (NHLBI) Grant for “Multi-ethnic Multi-level Strategies and Behavioral Economics to Eliminate Hypertension Disparities in LA County.”

Congratulations to Drs. Arleen Brown, Alejandra Casillas and Soma Wali who were awarded  funding from the NHLBI for the 4-year implementation phase of the UCLA DECIPHeR Study: “Multi-ethnic Multi-level Strategies and Behavioral Economics to Eliminate Hypertension Disparities in LA County.” Dr. Brown shares that this project builds on a 3-year planning phase, in which researchers collaborated with leaders and patients in the Los Angeles County Department of Health Services (LAC DHS), community representatives, community-based organizations, and a multidisciplinary research team to develop strategies for improving blood pressure control and reducing disparities in diverse patients with hypertension. Over the next four years, they plan to test the impact of these community-partnered, behavioral science-informed implementation strategies in a cluster randomized crossover trial to examine adoption and sustainment of culturally tailored and behavioral science-informed evidence-based practices and health-related outcomes

Arjun Deb, MD Awarded R01 for Study, “Targeting an ectonucleotidase in the heart with a monoclonal antibody to prevent post-infarct heart failure”

Professor of Medicine in the Division of Cardiology Dr. Arjun Deb has been awarded a $3 million R01 grant from the National Heart Lung and Blood Institute (NHLBI) for the study titled, “Targeting a ectonucleotidase in the heart with a monoclonal antibody to prevent post-infarct heart failure.” Dr. Deb shares that fibrotic diseases of the heart, liver and other vital organs constitute nearly 60% of all diseases affecting vital organs. Despite the immense importance of fibrosis, no specific therapeutic agents have been developed to prevent fibrosis in the heart or other vital organs. The grant will help his laboratory pursue specific antifibrotic therapies based on modulation of metabolic activity in the heart.

“Despite diverse diseases affecting different organs, fibrosis remains a common hallmark and it has been long debated that common pathways regulate scarring in multiple organs. This grant will help us to develop specific therapeutics for treating fibrosis in multiple organs”

states Deb, principal investigator on this grant and director of the UCLA CV theme.

Mitchell Wong, MD, PhD Awarded R01 from the National Institute on Aging (NIA) for, “A Natural Experimental Study of the Impact of Education on Physiologic Health, Stress, and Resilience and the Role of Socioemotional Factors”

Mitchell D. Wong, MD, PhD, professor of medicine in the division of general internal medicine and health services research, received a R01 grant from the National Institute on Aging to examine the underlying mechanisms of how education influences health over the life course. While education is thought to be a social determinant of health, growing evidence suggests that climbing the socioeconomic ladder (striving) may improve health for some (thriving) but impair health for others. In 2013, Dr. Wong and his team began a natural experiment, the Reducing Inequities in Social and Educational follow-up (RISE Up) Study, funded by NIDA (National Institutes on Drug Abuse), following a cohort of teenagers who entered the admission lottery of several high-performing charter high schools in low-income neighborhoods of Los Angeles. In prior studies of this cohort, published in JAMA Pediatrics and JAMA Network Open, researchers found the impact of improved education on self-reported health and health behaviors was immediate, substantial, and persistent beyond adolescence. By age 21, those who had attended a high-performing high school had a 50% lower rate of alcohol use disorder, 40% reduction in reporting fair or poor physical health, and 33% reduction in obesity/overweight. However, the improvements in physical health and obesity were only among males. Among females, attending high-performing schools was associated with lower rates of alcohol use disorder, but substantially worse physical health and obesity. Improvements in educational outcomes occurred in both males and females and did not explain sex differences in health outcomes. This new grant will allow Dr. Wong and his team to continue following the RISE Up cohort from age 24-28 and examine sex differences in the relationship between striving and thriving. They will measure the effects of striving on metabolic and psychological stress, coping, epigenetic aging, and gene expression profiles of physiologic resilience. Results of this study will help elucidate how overcoming poverty and adversity impacts health over the life course.

Total support for the RISE Up study is $8.5M including R01 funding from the National Institute on Drug Abuse, a seed grant from the UCLA Norman Cousins Center, and this new award of $2.5M from the National Institute on Aging. Co-investigators include Rebecca Dudovitz (Pediatrics), Teresa Seeman (Medicine), Steve Cole (Psychiatry), Janet Tomiyama (Psychology), and Nick Jackson (Medicine).

Congratulations to the UCLA Resource Centers for Minority Aging Research (RCMAR) Center for Health Improvement for Minority Elders (CHIME) Program

Congratulations to the NIA funded UCLA Resource Centers for Minority Aging Research (RCMAR) Center for Health Improvement for Minority Elders (CHIME) for the 2023-28 competitive renewal award. Continuously funded since 2002, the UCLA RCMAR CHIME is a research and mentoring program that contributes to the reduction in health disparities for minority elders by training under-represented faculty who will advance their careers by conducting minority aging research.  Co-funded by the UCLA CTSI since 2011, scientists are awarded pilot funds and participate in various mentoring activities and educational programming, including monthly seminars on relevant research and career development topics, a biannual scientific retreat, and an annual national meeting that convenes scientists from 17 other NIA funded RCMAR sites across the country.  The UCLA RCMAR CHIME continues this important work alongside long-standing and highly successful collaboration with community partners across Los Angeles County and Charles R. Drew University of Medicine and Science (CDU), while also developing an additional partnership and collaboration with the University of California at Riverside (UCR), a Hispanic Serving Institution (HSI) with expertise in training Hispanic students and those from other under-represented groups.  Led by Drs. Carol Mangione and O. Kenrik Duru (Alumnus 2004), the program directors and advisors include Drs. Keith Norris, Ron Hays, Catherine Sarkisian, Gerardo Moreno (Alumnus 2010) at UCLA as well as Homero del Pino (Alumnus 2015) from Charles Drew University, Gery Ryan from Kaiser Permanente Bernard J. Tyson School of Medicine, and Luisa Blanco (Alumnus 2013) from Pepperdine University.  We welcome new leadership as well, including Drs. Brandon Brown (Alumnus 2016) from UCR and Cynthia Gonzalez from CDU.  Drs. Kimberly Narain (Alumnus 2019) and Carlos Oronce (Alumnus 2022) from UCLA also join the leadership team as near-peer mentors.

From 2002 to the present, the RCMAR CHIME program has helped develop 68 Scientists from under-represented minority groups, 44% were Hispanic, 31% were African American, 25% were from under-represented Asian subgroups such as of Korean, Vietnamese, Filipino, Afghan, Iranian, Pakistani descent, and 75% were women scientists.  Among the 68 RCMAR CHIME Scientists, an unprecedented 91% have careers in academia, 3% in government and 6% in the non-profit sector.  Seventy percent have had subsequent federal grant support and among that group 26 have had support from NIA.  In the most recent cycle (2018-23), 18 scientists were awarded over $17.5M in follow on funds from NIH, private, and state/local funders and published 154 manuscripts. Over the past 20+ years, the Program has worked with scientists who are now prominent researchers in the DOM including Drs. Arleen Brown (2003), Jose Escarce (2004), Nina Harawa (2008), Alejandra Casillas (2018), Adriana Izquierdo (2012), and in other departments and schools including Drs. Medell Briggs-Malonson in the Department of Emergency Medicine and UCLA Health HEDI, Ninez Ponce (2004) Chair of Health Policy and Management, the UCLA Fielding School of Public Health, and Sarah Choi (2013) Professor in the UCLA School of Nursing, to name a few. 

The Call for Pilot Award Applications for 2024-25 will go out this Fall. Learn more and visit on the web at https://chime.med.ucla.edu/. 

Lauren Wisk, PhD Awarded Innovative Clinical or Translational Science Award from the American Diabetes Association

Dr. Laurent Wisk is an assistant professor in the division of general internal medicine and health services research who was awarded a 3-year $600,000 grant from the American Diabetes Association. Dr. Wisk shares that one-in-four youth in the US are currently living with prediabetes, most of whom don’t even know they have prediabetes, and those with social or economic disadvantages are even more likely to be affected. Without intervention, prediabetes is likely to progress into type 2 diabetes within 10 years. With lifestyle changes and weight loss, prediabetes can be reversed. However, adolescents/young adults (AYA) are the least likely to access proven diabetes prevention programs that can help them reduce their diabetes risk and build a healthier future. This purpose of this study is to address this missed opportunity for prevention by testing youth-focused enhancements to the delivery of diabetes prevention programs for vulnerable AYA. To achieve this goal, investigators will test program enhancements (developed with input from key stakeholders across campus) to determine if they are effective at helping AYA to enroll in the program, stay in the program, and make positive lifestyle changes during the program. Investigators will then follow-up with successful participants to understand how this program can be successfully implemented in other settings. Prevention is key, and targeted prevention earlier on in someone’s life has the opportunity to create the maximum impact across their life course. This project can make a significant contribution to how diabetes prevention is done. Moreover, it will help to ensure that prevention efforts are started as early as possible and that those efforts are directed to people who are most at risk of experiencing long-term impacts on their health.

“Although the CDC’s Diabetes Prevention Program has been extremely successful in reducing the risk of developing type 2 diabetes among individuals with prediabetes or other risk factors, this program has been largely unable to attract younger participants who could benefit greatly from this program. By making key modifications that will make this program more attractive and accessible to undergraduate students, we are hopeful that we can expand proven prevention strategies to reach younger populations,”

states Wisk.

Melissa Lechner MD, PhD Awarded Doris Duke Foundation Grant to Minimize Immune Reactions Created by Cancer Immunotherapy Treatment

Dr. Melissa Lechner, an assistant professor in the division of endocrinology, diabetes, and metabolism received a $495,000 grant from the Doris Duke Foundation to help develop strategies to minimize the harmful immune reactions some people diagnosed with cancer experience when undergoing immunotherapy treatment. Dr. Lechner shares that up to 60% of cancer patients treated with immune checkpoint inhibitors develop immune related complications resulting in treatment interruptions, hospitalizations, or sometimes death. This type of immunotherapy has been shown to significantly improve outcomes for patients with advanced cancers. With the support of the Doris Duke Foundation, Dr. Lechner will seek to better understand the underlying mechanisms that result in autoimmune complications and identify how to prevent or reduce these side effects.

“The cause of autoimmunity in healthy tissues is still not well understood. We are hopeful that by learning more about how autoimmune toxicities work, that we will not only develop strategies to reduce these side effects in patients treated with cancer immunotherapy, but also identify targets for the treatment of a broad number of autoimmune diseases,”

states Lechner.

I hope you are as proud as I am for our faculty success, in achieving new federal grant funding. We have updated last week's report listing federal awards in the DoM to include multiple principal investigators who are leading applicable projects. I encourage you to re-visit the page and learn who they are HERE.

Stay tuned for summaries in the future of our successes in clinical trials and foundation grant support.Keep the rain falling and let me know of your successes as you learn about them!

Each week, DoM faculty are invited to speak with local and national media about many of the most pressing medical and public health challenges faced around the world. I am pleased to highlight some of these interviews in our new “In the News Section.” Check back each week and hear how our faculty are raising awareness about their research to our local and national community and the significant impact of these efforts in society and the world.

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Dale

P.S.

For those who had no clinical duties, I hope you had an enjoyable Labor Day w/e with your families. For those who stayed in town, I hope the rain did not dampen your activities too much. I heard that rain wreaked havoc in Nevada at the Burning Man festival. So keeping with the theme of rain, I am including an interesting picture of what it could look like if it was raining people. That’s me and my wife in the center. If you can guess where this picture was taken, let me know!

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