1. < Cardiology/Epi

In the past few weeks, I have received a flood of notifications from faculty members sharing with me the news of successfully funded research grants (mainly from federal sources) that they will be receiving. I cannot put all these reports in this week’s email but will share more in next week’s email as well! The news was impressive and demonstrates the ways in which our faculty continue to push the envelope of innovation and successfully compete for these highly competitive grant awards. The stories shared in this post, is a sample of some of this news and reflect awards that will show up in our books during the new fiscal year that started on July 1. Therefore, we have also included a look back at the last fiscal year to summarize our successes in FY 22-23, in obtaining new federal grant support. It is important to note, that the data included in the FY22-23 summary, lists funding from the following federal sources: National Institutes of Health (NIH), the Department of Defense (DoD), the National Science Foundation (NSF), US Department of Agriculture and Health Resources and Services Administration (HRSA). They do not include funding from the Department of Veterans Affairs (VA), which will be reported separately in the future.  Similarly, industry-sponsored clinical trials and foundation awards will also be reported separately in the future.

The path towards becoming an independently funded investigator is a long one and can be challenging. In our department, our faculty work closely with our trainees providing mentorship and guidance on how to identify and compete for funding support that has the potential to launch their research career.

Daniel R. Wang, MD Awarded a 2023 Goodman Luskin Microbiome Center Seed Fellowship Award

As such it is appropriate to start with one of our trainees, Daniel R. Wang, MD, a first-year clinical cardiology fellow, who earned a 2023 Goodman-Luskin Microbiome Center Seed Fellowship Award for his project titled, “Racial/ethnic disparities in cardiovascular risk amidst discrimination: a lipidomics, gut microbiome, and neuro-imaging analysis.” Dr. Wang’s research interest emphasizes Asian-American/Pacific Islander and Hispanic health disparities, with a focus on the intersections among structural, social, and individual determinants of health. With this award, he will build upon previous research conducted by Arpana Gupta, PhD, Tien Dong, MD, PhD, and Gilbert Gee, PhD which demonstrated that discrimination leads to changes in the brain-gut microbiome system that included inflammation and correlates with threat response, emotional arousal, and psychological symptoms.

Specifically, Dr. Wang shares that he will use lipidomics (a technique that measures multiple lipid species at the same time in a sample) to unite microbiome and serum lipid alterations in the setting of stress (using discrimination as a proxy). He aims to show that documented gut microbiome metabolite changes, such as those seen in Asian-Americans experiencing discrimination, lead to measurable increases in lipid subclasses known to cause or be associated with atherosclerotic cardiovascular disease (ASCVD), such as ceramides, lysophosphatidylcholines, and others. By using lipidomics, the research will go beyond the traditional lipid classes tested for in clinical lipid panels, to build a more complete picture of lipid pathways and their subsequent alterations. The goal of this research is to further demonstrate the role of the gut microbiome in the development of clinical ASCVD and build the foundation for future targeted interventions in the prevention and treatment of cardiovascular disease.

Jason Hong, MD, PhD Awarded KO8 NIH Career Development Award

Jason Hong MD, PhD is an assistant professor in the division of pulmonary, critical care, and sleep medicine, and a graduate of the UCLA STAR Program. While earning his PhD in the STAR program, he studied pulmonary hypertension in a preclinical model using single cell RNA sequencing (RNAseq) under the mentorship of Mansour Eghbali, PhD, in the department of anesthesiology and Xia Yang, PhD, in the department of integrative biology and physiology. Dr. Hong notes that pulmonary arterial hypertension (PAH) remains an incurable and often fatal disease characterized by irreversible vascular remodeling in the lungs with overlapping pathological features with cancer. 

A more comprehensive and integrated examination of altered genes and pathways at the tissue, single-cell, and spatial level in human PAH lungs is critically needed to advance our understanding of the shared mechanisms of PAH and cancer. With the support of his KO8 NIH Career Development Award, he seeks to identify and characterize novel cancer-related genes as candidate molecular drivers of PAH to lay the groundwork for future translational studies.

Melissa Y. Wei, MD, MPH Awarded R01 to Develop Scalable, Person-Centered Multimorbidity Index Using Electronic Health Records

Melissa Wei, MD, MPH  is an assistant professor in residence, in the division of general internal medicine and health services research. Her research interests focus on multimorbidity (the coexistence of multiple chronic medical conditions), integrating measurement, management, prevention, prognosis, and policy implications. This week she received news that she will be awarded a new Research Project Grant (R01) from the National Institutes of Health (NIH). Dr. Wei notes that most adults will develop multimorbidity by late adulthood, and this is associated with an increased risk of poor health outcomes such as functional decline, poor health-related quality of life, hospitalization, and premature mortality.

However, current measures of multimorbidity have several limitations, such as a limited inventory of conditions based on billing data in hospitalized adults, that are not representative of diverse community-dwelling adults across the lifespan. The goal of this R01 project is to develop and assess the validity of a new, scalable, person-centered multimorbidity index using electronic health record (EHR) data from all the University of California health systems. Melissa’s team will assess the performance of the EHR-based multimorbidity index by testing its ability to predict key health outcomes.

“The proposed project is a transformative step for multimorbidity in clinical research and applications. I anticipate results will be directly applicable to improve the health of diverse, aging, vulnerable adults with multimorbidity,” states Wei.

states Wei.

Thanh H. Neville, MD Awarded R01 in Support of 3 Wishes Program

Associate Professor Thanh H. Neville, MD, from the division of pulmonary, critical care, and sleep medicine, received a $2.5 million NIH Research Project Grant (R01) in support of the 3 Wishes Program (3WP). Dr. Neville shares that dignified and compassionate end-of-life (EOL) care is a cornerstone of high-quality, patient-centered care, but EOL care is often overlooked, considered too late, or not at all. By eliciting and implementing final wishes for dying patients, the 3 Wishes Program (3WP) has demonstrated, in tertiary academic centers, that acts of compassion can improve the EOL experience and help families cope with loss.

For this grant, she will implement and evaluate the 3WP in the safety-net hospitals of Los Angeles, where there are less resources and more diverse, disadvantaged patient populations. Initially, she will obtain stakeholder input to customize a multi-component 3WP Toolkit that will facilitate 3WP implementation. Then, using this tailored 3WP Toolkit, she will implement and evaluate the 3WP at Harbor-UCLA, LA General, and Olive View-UCLA. Researchers will use a before and after study design to evaluate the effect of the 3WP on the quality of EOL ICU care, bereaved families’ psychological symptoms, and clinician burnout as compared to usual care.

“I cannot express how excited I was to receive this notice of award! I have always been passionate about improving end of life care in the ICU, and this grant will allow me to bring the 3 Wishes Project to hospitals outside of UCLA. I am particularly thrilled that this study will bring a palliative care intervention to a patient population that is underserved and often left out of research,”

states Neville.

Congratulations Thanh. I know that it was a long journey to get this award, but your tenacity, persistence and commitment to supporting end of life care has now received the recognition that it deserves!

Yusuke Tsugawa, MD, PhD Awarded R01 to Study How Diversity in Medical School, Residency Program, and Health System Board Affects Racial and Ethnic Disparities in AD/ADRD Care

Yusuke Tsugawa, MD, PhD is an associate professor of medicine in the division of general internal medicine and health services research. His research focuses on determinants of the quality and costs of care of individual physicians. This week, he learned that he has received his third NIH Research Project Grant (R01)! This recent award totaling nearly $2.7 million, will support a study examining how diversity in medical schools, residency programs, and health system boards impact racial and ethnic disparities in Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) care. Yusuke shares that high-quality care throughout the trajectory of illness of AD/ADRD has been shown to be associated with a better quality of life, lower caregiver distress, and reduced use of acute and long-term care. However, racial and ethnic minoritized persons with AD/ADRD often receive poorer quality care than White patients, including lower rates of advance directives, reduced receipt of anti-dementia medications, and increased end-of-life hospitalizations. Although physicians and health systems play an important role in providing high-quality care, little is known about how racial and ethnic diversity in physicians’ training environments and health system boards affect racial and ethnic disparities in AD/ADRD care.

The proposed study will address these important knowledge gaps by analyzing the comprehensive data on patients, physicians, medical schools, residency programs, and health systems by linking 7 nationally representative databases. In the first part of his study, the team will investigate how the racial and ethnic diversity of medical school students, where doctors graduated from affects care disparities using the changes brought about by state affirmative action bans; thereby, using the state affirmative action bans as a “natural experiment.” These bans affected student diversity of medical schools and provide a unique way to understand the impact of medical school diversity on AD/ADRD care disparities. 

In the second part, researchers will examine the effect of various factors of residency programs, such as the racial and ethnic diversity of residents, on care disparities. In the third part, they will investigate how the racial and ethnic composition of health system boards affects care disparities.

If proposed aims are achieved, this study will provide a robust evidence base for policymakers to develop policy interventions, such as increasing diversity in medical schools, residency programs, and health system boards, that may effectively mitigate racial and ethnic disparities in AD/ADRD care.  

“We are grateful to the NIH for providing us with the opportunity to conduct this important work. Their support allows us to investigate how diversity in physicians' training environments and health systems affects the provision of care to racially and ethnic minoritized patients with Alzheimer's disease, particularly in relation to racial and ethnic disparities,”

states Tsugawa.

Rajat Singh, MD, MBBS Awarded R01 for Nutrient Signaling at ER-Mitochondrial Contacts and Age-Related Mitochondrial Dysfunction Study

Professor of Medicine in the Division of Digestive Diseases Rajat Singh, MD, MBBS celebrates award of an NIH Research Project Grant (R01) of $1,967,291 in support of the project, “Nutrient Signaling at ER-Mitochondrial Contacts and Age-Related Mitochondrial Dysfunction.” Dr. Singh shares that mitochondria are essential energy-producing organelles known to lose their function with age—causing a number of age-related diseases. Mitochondrial well-being requires proper mitochondrial shape maintained through a process of mitochondrial division and fusion and that is mediated by various protein factors. Intermittent fasting helps maintain overall health, but we do not know if and how fasting itself impacts mitochondrial division and function with age.

His studies show that the typically nutrient-sensing mTORC2 pathway is paradoxically reactivated by fasting, and that this mTORC2 activation supports mitochondrial division and health. His preliminary studies also show a decline in mTORC2 activity with age. His team’s published studies show that during fasting, mTORC2 maintains mitochondrial division and health by engaging with previously undescribed downstream factors. If and how the ability of mTORC2 to interact and stimulate these factors is affected with age is not known. It has long since been shown that the clinically available mTOR inhibitor, rapamycin, extends healthy aging and lifespan by inhibiting mTORC1 signaling.

However, long-term rapamycin use tends to inhibit both mTORC1 and mTORC2. Because they propose that mTORC2 is key in keeping mitochondria healthy, the proposal argues that benefits of long-term mTORC1 inhibition with rapamycin are counterbalanced by concomitant mTORC2 inhibition—causing mitochondrial dysfunction. This forms the basis to explore if blocking mTORC1—in conjunction with maintaining mTORC2 activity—will lead to increased longevity. Based on initial observations, the team propose that mTORC2 inactivity and its failure to engage with downstream factors causes age-related decline in mitochondrial health. In this grant, Singh and colleagues will study how mTORC2 activity and its ability to support mitochondrial health are affected with age and during obesity. They will also study if simultaneous mTORC1 suppression by rapamycin, and stimulating mTORC2 through a number of new approaches, will lead to better health during aging than when rapamycin is used alone. These studies may help us understand how mTORC2 signaling can be leveraged to support mitochondrial function and healthy aging. Congratulations Rajat. Pleased to have recruited you to UCLA last year and to see how you have hit the ground running!

UCLA Cardiac Arrhythmia Center Awarded $11.5 Million NIH Program Project Grant (PPG) to Study Basic Mechanisms of Cardiac Arrhythmia and Neuromodulation

Kalyanam Shivkumar MD, PhD, professor of medicine & director of the UCLA Cardiac Arrhythmia Center & EP Programs, will lead a multidisciplinary team on the PPG titled “Cardiac Neuromodulation: Mechanisms and Therapeutics.” Individual project leaders on this grant include Olujimi Ajijola, MD, PhD at UCLA and Robert Harvey, PhD at the University of Nevada, Reno. UCLA investigators on this grant include Drs. Jeffrey Ardell and Zhilin Qu.

Decades of research shows that imbalance in the nervous system control of the heart contributes to the initiation of lethal arrhythmias. These arrhythmias are common and are thought to be responsible for the vast majority of sudden cardiac deaths worldwide (almost 12 million deaths/year worldwide). This is especially true after an initial injury to the heart, for example, a heart attack. This makes cardiac neuromodulation, the use of devices or other therapeutic approaches targeting the nervous system for cardiac benefit, an attractive option.

This multi-institutional National Heart, Lung, and Blood Institute grant will investigate the use of Vagal Nerve Stimulation and other approaches to achieve cardiac neuromodulation with the aim of translating this to the clinical arena for patients with heart attack or heart failure.

"The UCLA Cardiac Arrhythmia Center was created to provide exceptional patient care and perform cutting edge research that is needed to answer big questions about lethal arrhythmias," said study principal investigator Dr. Shivkumar, the founding director of the UCLA Cardiac Arrhythmia Center, and professor of medicine in cardiology, radiology and bioengineering. 

He adds,

"this grant will enable us to build on the journey started in 2002 and has fostered the careers of several physician scientists and scientists."

The PPG includes three interrelated research projects, with investigators focusing on such areas as the fundamental aspects of how nerves interface with heart tissue, ion channels affected by neurotransmitters and the effect of heart disease on triggering inflammation in neural structures that are involved in cardiac control.

"Fundamental insights regarding the progression of heart disease will be discerned with this effort,"

said Dr. Ajijola, associate director of the UCLA Cardiac Arrhythmia Center.

Join me in celebrating our colleagues who are leading these innovative federally funded research projects that will continue to advance the field of medicine. As I was receiving news of the awards highlighted above, I looked back over the past fiscal year (FY23) and note that the DOM received 34 new federal grants where the principal investigator was based at UCLA, so this year we are already off to an amazing start. The total support from those new federal awards in FY23 is $32,470,371! I invite you to learn about these grant awardees and their projects by clicking HERE.

The list shown only includes newly funded awards in the previous fiscal year and does not include funds received from ongoing existing awards. The $32.4M total does not include the multi-year HIV-focused research grant being led by Vice Chair of Research Judith Currier, whose federal contract was recently awarded additional funding, which if included, brings our department new funding total in FY 23, to $70,032,262!

Go Bruins! You are truly rockstars!

Yanina Venegas Appointed Chief Administrative Officer of the DoM

RSVP Deadline Approaching: DMPG Annual Meeting

This is the final reminder to RSVP for the DMPG Annual Meeting scheduled on Thursday, October 5th, which will include presentations by the leadership of UCLA Health. If you have not yet registered for the meeting, please do so by clicking below.

Dale

P.S. 
Last week I shared via email news of a lifetime achievement award that I received from the Endocrine Society. I received many kind notes and well-wishes from many colleagues within the DoM. I want to thank all of you personally for your support, which means a lot to me and my family.

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