ADVANCING TRANSLATIONAL IMMUNOLOGY
Otto O. Yang, M.D., a physician-scientist and a world expert on cellular immunology, has focused his research on viruses, immunology, and T cells for more than 25 years. He joined the UCLA faculty in 1999, received tenure in 2004, and serves as Professor of Medicine in the Division of Infectious Diseases, David Geffen School of Medicine at UCLA, with a joint appointment in the Department of Microbiology, Immunology, and Molecular Genetics. He is the Associate Chief of the Division of Infectious Diseases and Associate Director of the AIDS Institute at UCLA. His laboratory specializes in T cell immunology in HIV infection relevant to developing immune therapies and vaccines for HIV and other viral infections, with applications to other diseases such as organ transplantation and cancer. The unifying theme of his research is to understand the principles of immunity useful for vaccines and immunotherapy development.
After receiving his medical degree from Brown University School of Medicine, Dr. Yang pursued an internship and residency in Internal Medicine at Bellevue Hospital, New York University. During residency, his interest in infectious diseases and HIV-1 pathogenesis was ignited because more than 50 percent of his patients were infected with HIV-1. He pursued subspecialty fellowship and postdoctoral training at Massachusetts General Hospital and Harvard Medical School, where he developed a research program studying the role of CD8+ T lymphocytes (CTLs) in HIV-1 pathogenesis. CTLs are killer T cells that can destroy abnormal cells, such as those infected with viruses or transformed into cancer. CTLs are known to provide critical protective immunity for most viral infections ranging from herpes simplex to influenza. Dr. Yang’s work was among the earliest to delineate the protective role of CTLs in HIV-1 infection, leading many vaccine efforts focused on promoting anti-HIV-1 CTL responses. His work has since focused on understanding the eventual failure of CTLs to prevent AIDS, exploring the basics of the interplay between CTL antiviral function and HIV-1 evasion through mutation and effects on cells. His projects range from controlled in vitro models of CTL-HIV interaction to clinical observational studies.
Expanding from this basis of his studies in immunopathogenesis, Dr. Yang has contributed to principles such as chimeric antigen receptor gene therapy, or CAR T-cell therapy, which has revolutionized treatments for leukemias/lymphomas in recent years. CARs are artificial receptors that can retarget CTLs, key components of all HIV cure research. He is currently applying CARs to blood stem cells to treat viral infections and cancers. Dr. Yang authored the second paper published on CARs against HIV-1 and has patented multiple CARs that target HIV-1 and cytomegalovirus, which causes serious disease in persons with compromised immune systems.
While doing all this research, Dr. Yang remains an active infectious diseases clinician, treating patients at UCLA hospitals and clinics.
CTLs are broadly relevant to many diseases, and the principles Dr. Yang has studied have broad applicability. Relevant to design of effective immunotherapies and vaccines for HIV-1, which must improve on the natural failure of CTLs, he has developed experimental systems to delineate mutational options that the virus uses to evade CTLs, to look for viral vulnerabilities for immune targeting.
A more recent research interest has been the role of CTLs in transplanted organ rejection in patients. CTLs evolved to kill cells with foreign proteins, such as viral proteins, but transplanted organ cells also contain “foreign” proteins. Dr. Yang evaluated the key role of CTLs in rejecting transplanted lungs, and in collaboration with the new composite tissue transplantation program at UCLA established for hand and face transplants, recently showed that only a very limited population of CTLs cause rejection of transplanted hands. This lays the groundwork for targeted strategies to prevent organ rejection, rather than the current nonspecific immunosuppressive treatments that suppress all T cells and render patients vulnerable to life-threatening infections.
Before being swept into HIV-1 research by the AIDS pandemic during his clinical training, his initial plan was to be a cancer researcher, and he has brought his work full circle to oncology. He has very recently begun working on principles for CTL based treatment of cancers caused by Human Papillomavirus (HPV), which causes cervical cancer, anal cancer, and head/neck cancers.
Given his expertise in viruses and role as an infectious diseases physician, he was uniquely positioned to explore treatments and immunity to SARS-CoV-2, and he has been a leader in clinical trials for new treatments at UCLA and basic research on this virus.
Finally, relevant to treating viral infections and cancers with CTL therapy, Dr. Yang has been working on methods to use blood stem cells to create a continuous and permanent source of desired CTLs in patients.
SOME OF DR. YANG’S ACCOMPLISHMENTS
- Serving as lead UCLA investigator on nine clinical trials for the treatment of severe COVID-19, leading to establishing the efficacy of treatments such as remdesivir and baricitinib
- Training and mentoring the next generation of translational immunologists and physician-scientists, with prior trainees continuing at prestigious institutions such as UCLA, Harvard, and Cornell
- Co-founding a biotech startup company
- Generating three patents and 10 provisional patents for his inventions
- Garnering nearly $30 million in grant funding through more than 60 competitive government research grants
- Publishing more than 170 peer-reviewed articles in prestigious journals
- Serving as an expert grant reviewer for the National Institutes of Health and multiple foundations
- Reviewing publications for over 50 scientific journals
- Being a key public presence as an infectious diseases expert on the COVID-19 pandemic for news organizations such as CNN, and periodicals such as The Wall Street Journal, the New York Times, and Time Magazine
Inquiries about the work of the Yang Immune Innovation Fund may be directed to Dr. Yang at: (310) 791-9491 or [email protected].
Inquiries about donating to the Immune Innovation Fund may be directed to Gretchen McGarry, Executive Director, UCLA Heath Science Development at (310) 794-4746 or [email protected].
Your tax-deductible donation may also be made via this link: http://giving.ucla.edu/immune-innovation.
Thank you for your support of the Yang Immune Innovation Fund