Graduate Studies Faculty
Jonah B. Sacha, Ph.D.
Programs:Molecular Microbiology & Immunology
Program in Molecular & Cellular Biosciences
Research Interests:HIV T cells Antigen Processing and Presentation Endogenous Retroviruses » Click here for more about Dr. Sacha's research » PubMed Listing
Preceptor RotationsDr. Sacha has not indicated availability for preceptor rotations at this time.
Faculty MentorshipDr. Sacha has not indicated availability as a mentor at this time.
With more than 20 million dead and greater than 30 million currently infected with HIV, development of a prophylactic HIV vaccine is a top global health priority. However, despite 30 years of intense research there is no vaccine and new approaches are urgently needed.
Viral sequence diversity is the Achilles’ heel of traditional vaccine approaches to HIV and poses one of the greatest hurdles to vaccine development. The Sacha laboratory aims to determine which antigens should be targeted to overcome the formidable obstacle of HIV viral sequence diversity. Thus, we are actively exploring three distinct, but related areas of immunity to highly variable pathogens such as HIV:
CD4+ T cells
While the role of CD8+ T cells in AIDS virus infection is well documented, much less is known about antiviral CD4+ T cell responses. However, understanding the precise immunological role played by CD4+ T cells during retroviral infections will provide insight into the components of an effective immune response and is a key step in facilitating rational vaccine design. Furthermore, CD4+ T cells are able to tolerate extensive sequence diversity in their target epitopes, raising the possibility they might be particularly effective in immunity to hyper-variable pathogens. We are actively pursuing how CD4+ T cells contribute to the control of genetically diverse pathogens like retroviruses.
Non-HIV targets for protection: Endogenous Retroviruses
The genome of every human being contains endogenous retroviruses (ERVs), which are the genetic fossil remains of ancient retroviral infections that integrated into germ line cells. Although normally quiescent, ERVs are active and targeted by the immune response during infection with pathogens such as HIV and in disease states like cancer. Because ERV-specific immune responses arise only during pathological processes, they may represent an alternate, stable target for vaccine-induced immunity. We are exploring the role of ERVs in immunity to disease to understand how to exploit these germ-line sequences for protecting the host from viral infection and disease.
A rare subset of infected individuals will contain viral replication to undetectable levels and do not progress to AIDS even without antiretroviral treatment. These rare individuals offer a glimpse into effective anti-AIDS virus immunity. Interestingly, some of these individuals will spontaneously lose the ability to control the virus. We are studying the breakthrough virus in these individuals to delineate correlates of protection from infection with a chronic virus like HIV.