Year 2. January 30. Research, Scholarship, and Advocacy form the Lab to Society

Youth Living with HIV in Sub Saharan Africa

Prior to joining us in the department of medicine as a med-peds resident, Kalei Hosaka, MD, spent nine months in Tanzania, studying how youth living with HIV manage stigma and the sense of belonging in their community. Approximately four million youth around the world live with HIV, 85% of whom live in sub-Saharan Africa. While there is significant U.S. based research about stigma, Dr. Hosaka and his team sought to examine it from the local Tanzanian perspective using a collaborate arts approach that engaged youth and community organizations in his research.

Using artwork creation, prompts, and qualitative interviews, Dr. Hosaka partnered with youth to discuss their experiences with stigma and the concept of belonging while growing up with HIV. Youth discussed challenges and trauma, as well as their hopes for a better future. In his publication “‘I am not alone with tears’: embodying stigma and longing among youth living with perinatally acquired HIV in Tanzania through a collaborative arts-based approach,” Dr. Hosaka describes that among the youth interviewed, stigma changed over time as youth got older and new interventions and medical advancements are made. 

Youth also expressed that they do not feel alone in their suffering. There is a sense of solidarity within their community, and that while stigma continues to exist, they feel empowered to reframe others’ perception of them, as well as pursue dreams for the future.

“As we talk about leading community engaged work, a collaborative arts approach allows us to partner with others and really listen to their voices, build solidarity, walk with people through both joy and suffering. We are in a field where there not only is a lot of hurt but also a lot of hope,” states Dr. Hosaka.

states Dr. Hosaka

In addition to the publication, Dr. Hosaka presented the paper as an art exhibit at the AIDS 2022 International HIV Conference, which took place in Montreal, Canada in July-August 2022. You can view the pictures below and read the paper in its entirety HERE.

Supporting Care Givers within Medically Underserved Communities

Utpal Sandesara, MD is a recent graduate of our Primary Care Residency Program in the Olive View Santa Clarita Track. Dr. Sandesara, who recently published his first book, has joined our faculty in the division of general internal medicine, based at Olive View Hospital. He has hit the ground running and is the recent recipient of a UC END DISPARITIES Pilot Award from our CTSI P50 Grant.

The proposal entitled “Experiences and Needs of Informal Caregivers for Multiethnic Patients with End-Stage Liver Disease in a U.S. Urban Safety-Net Setting” addresses the role of informal care givers for patients with end stage liver disease in underserved communities.

End-stage liver disease (ESLD) is a major cause of suffering and death in the U.S., with significant outcome disparities along racial, ethnic, and socioeconomic lines. Caregiving is increasingly recognized as a crucial social determinant of health, but we know very little about the experiences of people providing unpaid care for patients with ESLD, particularly in contexts of poverty, linguistic/ethnic minority status, and limited healthcare access. This project will use ethnographic observation and longitudinal interviewing with caregivers and healthcare workers to develop deeper understandings of the roles, practices, experiences, and perspectives of caregivers for ESLD patients at Olive View-UCLA Medical Center, a hospital in the Los Angeles County Department of Health Services. Such understandings can guide changes that strengthen healthcare system-caregiver partnerships, enhance caregiver support, and reduce suffering for patients and caregivers.

Dr. Sandesara notes,

“As a sociocultural anthropologist, I believe in the power of ethnography - a longitudinal, person-centered research methodology - to transform our understandings of health disparities as lived experiences. This project, undertaken in partnership with a safety-net hospital and the community it serves, is an opportunity to generate insights that can inform clinical interventions and upstream policy changes with the potential to positively impact the lives of patients with ESLD and their caregivers.”

Understanding How Fat Cells can Regulate Metabolic Health

Obesity and overweight are increasing globally and contributing to many conditions that can limit health, lifespan and quality of life. Thus, fundamental research to understand how fat cells are regulated may ultimately identify new ways to treat or prevent obesity. Therefore, let me highlight a recent publication by one of our junior faculty  Zhenqi Zhou, PhD that was recently published in the journal Nature Communications.

Dr. Zhou identified Park2, the gene that encodes an enzyme, the E3 ubiquitin ligase Parkin, that is a critical regulator of fat cell expansion leading to obesity, defined as adiposity.  Selective reduction of Park2 expression protected mice against high fat diet-induced obesity and disruption of metabolic health. Dr. Zhou determined that Parkin plays a novel role in the turnover of a protein called Pgc1a, that regulates the ability of cells to increase their mitochondria in a process known as mitochondrial biogenesis.

The Zhou Laboratory, including work by Drs. Timothy Moore and Jennifer Ngo, and MCDB undergraduate researcher Alice Ma, showed that Parkin deletion increased mitochondrial genome copy number and stabilized numerous proteins known to improve mitochondrial function. These findings suggest that selective targeting of Parkin in adipocytes could be of therapeutic value to combat obesity and obesity-associated disorders.  Additional DoM faculty participating in this research include Philip Scumpia, MD, Orian Shirihai, PhD, Jake Lusis, PhD, Thomas Vallim, PhD, and Andrea Hevener, PhD.

Heart disease remains the leading cause of death worldwide and vascular disease linked to abnormal cholesterol represents an important risk factor. The relationship between how we absorb fat and risks for cardiovascular disease are incompletely understood. Therefore, I was pleased to learn of the recent 4-year award from the National Institutes of Health, "Targeting the gut-liver axis in cardiovascular disease." This grant providing $1.86M/yr. in support was just awarded to Associate Professors of Cardiology Elizabeth Tarling, PhD and Thomas Vallim, PhD. Here are some additional details provided by Drs. Tarling and Vallim about their study.

Cardiovascular Disease (CVD) is the leading cause of death in the US, and high blood cholesterol levels (particularly LDL cholesterol) accelerate CVD/atherosclerosis. The increase in CVD is also associated with people eating more fatty diets, which contain cholesterol and can therefore worsen blood levels of cholesterol. Dietary lipids, like cholesterol, are insoluble and require detergents (bile acids) for absorption. The production of these bile acid detergents in our bodies is controlled by the liver, but there are many types of bile acids and we don’t understand why we make different types and what they do. Our lab has discovered that changing the amount and the type of bile acids can change how much cholesterol enters our body, and therefore affect the development of atherosclerosis.

Dr. Tarling notes,

“Despite largely successful lipid lowering treatments, adverse events continue to rise. Increased dietary lipid intake is a major contributor to increased CVD disease burden and blood lipid levels. Our studies are advancing our fundamental understanding of how absorption and uptake of specific lipids regulates the progression of atherosclerotic disease. Furthermore, our studies may also reveal whether targeting absorption of specific lipids via changing bile acids can reveal novel opportunities for therapeutic intervention.”

Congratulations Liz and Tom!

Antibody Responses to COVID-19 Vaccines or Infection Informs Vaccine Efficacy

A team led by Otto Yang, MD, professor in the division of infectious diseases, recently published a paper in the journal ACS Nano, that provides new insights into antibody responses following COVID-19 Infections or vaccination.

After COVID-19, there is a highly variable level of antibodies that depends on the severity of illness, from very low levels after mild illness to high levels after severe illness, and this study was among the first to compare the antibody response to COVID-19 mRNA vaccination to natural infection. After the first vaccine dose, levels were similar to persons with mild illness, and the second dose achieved levels that were not as high as severe illness. However, people who previously had even mild COVID-19 achieved a maximum level after a single dose, which has important implications for saving vaccine doses when vaccines are in short supply. Finally, this study is one of the first to show that antibody levels drop rapidly after vaccination and predict that booster vaccinations would be needed to maintain protection.

Designer Cell-Based Treatments for Cancer

Antoni Ribas, MD, professor in the division of hematology and oncology, leads a research program in the DoM and the Johnson Comprehensive Cancer Center focused on harnessing immune cells to cure cancer.  In a recent publication in the journal Nature, they describe a novel approach to engineering patients T-Cells by genetically altering T-Cells with receptors that uniquely recognize mutations in their own tumors, that can then be infused back into these patients to specifically target their tumors.

In a phase 1 trial in patients with advanced cancers, CRISPR was used to insert new genes in immune cells, efficiently redirecting the immune cells to recognize mutations in the patient’s own cancer cells. When infused back to patients, these CRISPR engineered immune cells preferentially traffic to the cancer and become the most represented immune cells there. This study demonstrates the feasibility of isolating and cloning multiple immune cell receptors recognizing mutations in cancer cells in a patient personalized manner, the simultaneous knock-out of the endogenous immune receptor and knock-in of the redirecting immune receptor using single-step, non-viral precision genome editing, the manufacturing of CRISPR engineered T cells at clinical grade, the safety of infusing up to three gene edited immune cell products to patients, and the ability of the gene edited immune cells to traffic to the patients’ tumors.

This report garnered wide-spread press coverage in Nature,U.S. News, and the news sources below:

Research Project to Determine Efficacy for Individual Versus Group Coaching to Address Physician Burnout

We are recruiting DoM Physicians for Study Regarding Effectiveness of Professional 1:1 Coaching

Josh Khalili, MD is conducting a study on the potential benefits of coaching. Individuals will be randomized to determine whether professional 1:1 coaching compared to professional small group coaching is effective in reducing physician burnout. Over the next 30 days, researchers are recruiting up to 90 actively practicing UCLA Department of Medicine physicians (regardless of specialty) with at least two years of clinical experience as faculty. The expected time commitment for participants is 6 hours (split into six, 1-hour Zoom sessions) over 3 months. Please click HERE or on the link below for further information and to complete the Qualtrics survey to determine eligibility and express interest in participation. 

Closing Thoughts on the Importance of Maintaining a Focus on Confronting Forces that Drive Wedges Between Us.

The past week has been challenging for many of us. It seems like the frequency of gun violence is increasing in California and elsewhere in the country. We have witnessed senseless mass shootings, many targeting specific segments of our community, members of which have felt targeted and marginalized. This weekend marked the release of the video showing the beating of Tyre Nichols by police in Memphis. For many of us, events like this trigger complex feelings regarding the challenges of being black in America. The department is committed to creating a community that celebrates our diversity, is respectful of the differences that make us stronger, providing an environment where no one is excluded and striving to support everyone who is struggling with the consequences of fissures that are confronting us. February is Black History Month, and the department will host activities that will recognize unique contributions of African Americans to the fabric of our community and country.

Last Friday, January 27 marked International Holocaust Remembrance Day. The annual day of commemoration recognizes the liberation of Auschwitz-Birkenau concentration camp in 1945 and honors the six million Jewish victims of the Holocaust and other victims of Nazism. It was a day for us to reflect and reaffirm our commitment to fighting against intolerance and violence. Recently we have seen or experienced an increase in antisemitism and acts of violence towards targeted groups. As a community we stand against all forms of hate and commit to leading meaningful action that can guide us closer to inclusivity, diversity, and justice.

On February 6th, the Department of Medicine Professional Group will kick off the 2023 Annual DMPG Retreat. All DoM faculty are invited to attend the first session “Equity, Diversity, and Inclusion in the Department of Medicine,” hosted by DoM Vice Chair for Equity, Diversity and Inclusion Keith Norris, MD, PhD. The webinar begins at 12:10 pm. A reminder email will be sent out later this week.