1. < Message from the Chair

The broad-based contributions of our faculty to training the next generation of LEADERS from undergraduates to medical and graduate students, post-docs, residents and fellows is truly impressive. The dedication of our faculty and commitment to the next generation is inspiring. Their efforts have paid off, and this week I share with you accolades from students and trainees across the entire spectrum.

DoM Mentees Earn Top Prize at UCLA Undergraduate Research Week

At UCLA and the department of medicine (DoM), many of our faculty recognize that undergraduate students often demonstrate their investigative talents and analytical abilities long before they begin a graduate training program. It is our duty to support our student’s innate sense of curiosity and the development of critical skills which they use to build upon our understanding of medicine while pushing scientific frontiers.

Each year, UCLA’s Undergraduate Research Week provides a valuable platform to enable students to highlight their research achievements and celebrate their contributions to various disciplines. It is the largest undergraduate conference at UCLA with submissions accepted in 22 categories. I was pleased to see that our department faculty and postgraduate trainees are actively mentoring undergraduate students who presented at the conference, including seven who earned Dean’s Prizes for Excellence in Research: Life Sciences, Physical Sciences and Engineering. I share with you a few of the projects and reflections from the students and their mentors who earned this top distinction. Each had the opportunity to share their work during a livestreamed event featuring faculty-mentored research at the Undergraduate Research & Creativity Showcase.

Student	Project	Mentor
Charlie Zhi-Lin Zheng	Snai1b-Mediated Myocardial Growth and Trabeculation in Response to Mechanical Stimulation	Tzung Hsiai, MD, PhD Jing Wang, PhD

"Cardiac development is a fantastic process of extensive tissue remodeling seen across all higher vertebrates. The rudimentary heart, initially nothing more than a pulsating tube, transforms into a complex, 4-chambered machine with muscular walls that contract in marvelous synchrony and sturdy valves that enforce unidirectional blood flow. This intricately choreographed process can sometimes have errors, resulting in congenital heart disease (CHD), the most common congenital anomaly in the United States. As cardiac development is a complex process, CHD encompasses many cardiac anomalies, each caused by the failure of one or more of the countless cardiac developmental pathways.

As numerous as they are, these pathways are often not fully understood in their roles and mechanisms during development. For two years, I’ve worked with Dr. Hsiai and my direct mentor, Jing Wang, to study two specific processes of cardiac development: that of the muscular walls and the valves. In both studies, I used embryonic and juvenile zebrafish as a model of heart development and reached milestones in discovering new mechanosensitive pathways.

In our valve project, we have established the first morphological + transcriptomic timeline of the bicuspid-to-quadricuspid transition of the zebrafish atrioventricular (AV) valve. This process is also seen in early human heart development. Given their minuscule size, collecting the valvular tissue of juvenile zebrafish was a technically challenging and unprecedented effort. It took many months and wasted samples before I optimized a microdissection workflow, with which my direct mentor, Jing Wang, and I collected enough replicates from each timepoint for bulk RNA-sequencing. We are currently analyzing our transcriptomic findings and identifying genes that may drive this critical process in AV valve development, which also occurs in human hearts.

In our heart wall project, for which I was awarded a Dean’s Prize for Excellence in Science at the 2024 Undergraduate Research and Creativity Showcase, we have secured functional evidence for a novel pathway in trabeculation, a critical process in heart wall development, and identified a novel role for the Snail family of developmental genes (note: not the animal). We designed a CRISPR-based gene knockdown and overexpression system to produce this evidence, which took months and many failed trials to optimize. To study the mechanosensitive nature of our newly discovered pathway, I helped develop a 4D reconstruction algorithm for live zebrafish heart imaging – another unprecedented effort. We are currently finalizing this project and expect to submit our findings for publication within the following year.

Ultimately, our findings across both projects are steps toward future genetic therapy targets for CHDs. Our valve transcriptomic development timeline sets the stage for the discovery of potential targets. Meanwhile, our discovery of a specific developmental pathway in heart wall development may pave the way to future therapeutics for cardiac regeneration by targeting myocardial-specific Snail programs."

Student	Project	Mentor
Srihari Prabu	Ultrafine Particle Inhalation and Chronic Inflammation in Interleukin-10 Deficient Mice	Jesus A Araujo MD, PhD Louie Allen, PhD Candidate

We all hear about air pollution in cities and how bad it has become, but most people do not know exactly how bad air pollution is for human health. Air pollution has tiny particles that end up in the lungs and cause inflammation or injury that might not go away. Eventually, cells in our lungs and body will change, leading to heart disease. In this study, we examined how particles found in the air can cause inflammation using highly susceptible mice. We discovered that exposure to particles led to heightened inflammation in the lungs, while in the liver this response was the opposite, even reducing inflammation. It seems that our lungs are getting the most damage while the liver adapts and protects against the particles. To paint a clearer picture, we plan to do further experiments to determine how antioxidants play a role in defending against these air pollution particles.

Srihari’s mentor, Louie Allen, reflects on his experiences serving as a mentor and shares the following, “For as long as I can remember, I have always been surrounded by supportive mentors that were leaders in their field of research. They provided opportunities for me to explore my scientific interest, invested time and effort to help me achieve my goals and encouraged me to always take that next step in my journey.

Student	Project	Mentor
William Peter Harvey	Utilizing Barcoded HIV-1 to Examine the Effect of Envelope Tropism on HIV Reservoir Formation	Jocelyn Kim, MD Jerome Zack, PhD

HIV-1 is a virus that, in addition to actively replicating in infected cells, can establish a latent infection, known as the reservoir, that is undetectable by the immune system and incurable with modern antiretroviral therapy (ART). The viral tropism project was designed to assess how different coreceptors (CXCR4 and CCR5) used by HIV-1 to invade cells during acute infection affects the virus's ability to establish early latent cell populations in humanized mice. We developed two swarms of HIV-1, each containing a barcode tag within the viral genome. One swarm used the CXCR4 coreceptor and the other used CCR5 to initiate infection. After taking the infected mice off ART, we observed patterns that suggest that HIV-1 strains that use the coreceptor CCR5 create a larger latent reservoir and may directly outcompete CXCR4-utilizing HIV-1 strains during reservoir formation.

William shares the following about earning the Deans Prize, “Since joining the Zack Lab at the beginning of my junior year, I have grown immensely as both a student and a scientist due to the supportive mentorship of my supervisors and peers. My mentors, Dr. Jerome Zack and Dr. Jocelyn T. Kim, have continuously encouraged my passion for research and pushed me to achieve my academic and professional goals while providing an uplifting space for me to develop practical laboratory skills.

These are just three of the award-winning projects presented by students mentored by DoM faculty and post-graduate students. I invite you to view the list of the seven Dean's Prize winners projects, mentored by DoM faculty HERE and the full list of winners HERE.

Ye Yang (PhD Candidate) Awarded the Arnold J. Berk Research Achievement Award

In “APOA5 Deficiency Causes Hypertriglyceridemia by Reducing Amounts of Lipoprotein Lipase in Capillaries,” Ye led a fascinating presentation highlighting that APOA5 binds to a protein, the ANGPTL3/8 complex to suppress its ability to inhibit the hydrolase activity of an enzyme, lipoprotein lipase, which breaks down triglycerides bound to lipoproteins (LPL TG). In Apoa5-deficient mice, unbridled ANGPTL3/8 activity results in reduced amounts of LPL along the luminal surface of heart and brown adipose tissue capillaries. ANGPTL3/8 detaches LPL from binding sites on the surface of cells; the detachment of LPL can be blocked by recombinant APOA5 and by an inhibitory antibody against ANGPTL3/8. APOA5’s ability to bind and suppress ANGPTL3/8 is utterly dependent on the last ~40 amino acids of APOA5, explaining why mutations of APOA5 in humans, that shortens the protein (truncation mutations) cause severe elevation of circulating fat, which is called hypertriglyceridemia. An inhibitory ANGPTL3/8-specific monoclonal antibody mimics APOA5 function, preventing ANGPTL3/8-mediated inhibition of LPL activity and preserving amounts of LPL within capillaries.

Ye’s latest achievement is a small snapshot of her research achievements thus far. Her mentors include Drs. Loren Fong, Anne Beigneux, Michael Ploug, Robert Konrad, and Dr. Stephen Young who shared that Ye worked as a SRA in the Young Lab, prior to pursuing her PhD in human genetics. She has published 12 research studies and is described by her mentors as “diligent, with great technical skills, creativity and a commitment to high-quality data.”

Congratulations Ye, and thanks to your mentors!

Mehrdad Roustaei, PhD Awarded 1^st Place at LA Best Pearl Cohen Poster Competition

The Los Angeles Bioscience Ecosystem Summit Twenty 24 (LA Best) brought together nearly 1,000 participants from across the Los Angeles area to showcase bioscience innovation and scientific discoveries which may lead to future patient treatments. Representatives from the pharmaceutical and biotech industry, UCLA, Caltech, Cal State LA, City of Hope, USC and Cedars Sinai converged at UCLA on May 23, 2024, to highlight their translational research programs and start-ups. The summit includes the Pearl Cohen Poster Competition, which calls upon graduate students, postdoctoral researchers, and faculty to present across five themes that include cancer, cardiovascular and metabolism, immunity, inflammation, infection and transplantation (I3T), neuroscience and regenerative medicine.

I am pleased to highlight that a second mentee from the Hsiai Lab, Dr. Mehrdad Roustaei earned top honors at the Pearl Cohen Poster Competition bringing home 1^st place! Dr. Mehrdad’s award winning research "Exercise Mitigates Flow Recirculation and Activates Metabolic Transducer SCD1 to Catalyze Vascular Protective Metabolites," explores the mechanistic link between physical exercise and vascular health. He and other researchers discovered that exercise-induced pulsatile shear stress (PSS) activates the enzyme Stearoyl-CoA Desaturase 1 (SCD1) in endothelial cells. SCD1 catalyzes the production of anti-inflammatory lipid metabolites such as oleic acid and palmitoleic acid, which play a crucial role in mitigating NF-κB-mediated inflammatory responses and reducing vascular cell adhesion molecule-1 (VCAM1) expression. Additionally, this pathway helps reduce arterial stiffness, offering a promising therapeutic target for individuals with arterial stiffness due to hypertension who cannot undergo exercise training.

DoM Celebrates Graduates of the Residency and Physician Scientist Training Program

As a mentor, one of the proudest moments of the mentorship experience is witnessing our mentees graduate from their training programs after years of rigorous scientific and clinical training. Last week, mentors, families, and loved ones gathered at UCLA to celebrate our graduating class from the UCLA Internal Medicine Residency Program and the Specialty Training Advanced Research (STAR) Program. It was a joyous celebration which recognized the years of hard work and dedication which have led our trainees to becoming LEADERS who we are confident will lead a life of impact in the communities they serve.

STAR Graduation

We begin with the STAR Graduation Ceremony where six trainees earned PhD’s, in addition to their MD’s, after undergoing research training concurrent with clinical residency or fellowship. Since its inception, the STAR Program has graduated over 250 MD, PhD’s who have gone on to become leaders in academia, industry, government and nonprofit sectors. This year’s class includes:

This class includes a member who I have known since he was in high school. I was especially proud of Dr. Lawrence Benjamin who I first met as a high school student.  I experienced a full circle moment watching him graduate from the UCLA STAR Program under the mentorship of Dr. Carol Mangione. I know that Lawrence and these physician-scientists will go on to push the frontiers of scientific innovation and introduce us to bold, new concepts that will allow us to transform patient care.

I would also like to invite you to join me in celebrating Tomas Ganz, MD, PhD who is the recipient of the Alan M. Fogelman Research Mentorship Award. The Fogelman Award is the largest institutional award dedicated to supporting mentorship activities in the country. This year, we received a record number of nominations and the STAR Program Selection, along with external reviewers, selected Dr. Ganz as the honoree in recognition of his decades of mentoring over 60 mentees towards independent successful research careers. In his remarks, Dr. Ganz reminded us all that following science will always lead to discovery, the importance of valuing each team members contributions, prioritizing our mentees, and always being an equal team member. Dr. Ganz exemplifies the values and qualities that make the UCLA DoM a top destination for researchers to be bold, creative, and inclusive in their innovative pursuits.

DoM Residency Graduation

Next we celebrate our residents who after three years have concluded their internal medicine residency training and will be beginning new chapters in their medical careers. Last Friday, we gathered at the Centennial Terrace at the Luskin Center, to recognize our incredible trainees who are about to begin their careers as attendings or continue their training in fellowship programs. Last December, we shared where our residents pursuing fellowship training will be headed to NEXT. Today, I celebrate our residents who will be starting their first job after residency training! Take a look at where they are going next.

While our residents were training and providing exceptional patient care, they were also ensuring that those who are following in their footsteps receive a high-quality educational experience. Many of our trainees and faculty were recognized with teaching and mentorship awards which captures their commitment to innovative teaching strategies that stimulate interest in their specialties. I am pleased to recognize the following individuals who received awards from the Internal Medicine Residency Program. Please join me in celebrating:

Congratulations to all!

If you were not able to attend the virtual Internal Medicine Residency Program graduation, I invite you to view it here!

You may also view pictures from the celebration by clicking below.

Dale.

P.S.

On June 1, I had the privilege of receiving the life-time achievement award of the Endocrine Society, which came with a gold medal. My wife told me to keep this at home! Thanks to the UCLA faculty and trainees who joined me for a celebration dinner.

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