Dr. Sacha’s laboratory is engaged in research in three distinct, but related areas of T cell biology.
The obstacle of sequence diversity in vaccine design:
Viral sequence diversity is the Achilles’ heel of traditional vaccine approaches. For example, the influenza vaccine must change yearly in anticipation of the predominant circulating viral strains, which differ from one another by only 1-2%. The problem of viral diversity is exponentially larger in pathogens such as HIV, where co-circulating HIV strains can differ from each other by up to 35%. Indeed, the extraordinary sequence variation of HIV poses one of the greatest hurdles to vaccine development. New vaccine modalities are desperately needed to overcome this formidable obstacle. We are currently designing and testing novel approaches to solve the problem of viral sequence diversity.
Endogenous retroviruses in human disease:
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. These fixed retroviral sequences account for ~8% of the entire human genome and are inherited from parent to offspring like cellular genes. Although normally quiescent, ERVs can become active and are targeted by the cellular immune response during infection with pathogens such as EBV and HIV and in disease states like cancer. Because ERV-specific immune responses may arise only during pathological processes and are currently understudied, their role in immunity is likely greatly underappreciated. We are currently exploring the role of ERVs in pathogenesis and immunity.
CD4+ T cells in retroviral infections:
Cellular immune responses are a critical component for containing the replication of retroviruses such as HIV. While the role of CD8+ T cells in AIDS virus infection is well documented from CD8+ T cell-mediated viral escape and CD8 depletion studies, 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 likely provide insight into the components of an effective immune response and is a key step in facilitating rational vaccine design. We are actively pursuing how CD4+ T cells contribute to the control of retroviruses despite being the targets of the virus.
Dr. Sacha graduated cum laude from the University of Missouri-Columbia in 2003 with a B.A. in German and B.S. in Biology. After receiving his Ph.D. in Microbiology & Immunology from the University of Wisconsin-Madison in 2007, he joined the faculty at UW-Madison where he researched the characteristics of effective retrovirus-specific CD8+ and CD4+ T cells. In 2011, he joined the Oregon Health & Science University and has appointments in the Vaccine & Gene Therapy Institute and Pathobiology & Immunology Division of the Oregon National Primate Research Center.
Fujita T, Burwitz BJ, Chew GM, Reed JS, Pathak R, Seger E, Clayton KL, Rini JM, Ostrowski MA, Ishii N, Kuroda MJ, Hansen SG, Sacha JB, Ndhlovu LC. Expansion of dysfunctional Tim-3-expressing effector memory CD8+ T cells during simian immunodeficiency virus infection in rhesus macaques. J Immunol. 2014 Dec 1;193(11):5576-83. (doi: 10.4049/jimmunol.1400961.) [PMID: 25348621, PMCID: PMC4239185] Epub 2014 Oct 27.
Burwitz BJ, Reed JS, Hammond KB, Ohme MA, Planer SL, Legasse AW, Ericsen AJ, Richter Y, Golomb G, Sacha JB. Technical advance: liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease. J Leukoc Biol. 2014 Sep;96(3):491-501. (doi: 10.1189/jlb.5TA0713-373R.) [PMID: 24823811] Epub 2014 May 13.
Michaud HA, SenGupta D, de Mulder M, Deeks SG, Martin JN, Kobie JJ, Sacha JB, Nixon DF. Cutting edge: An antibody recognizing ancestral endogenous virus glycoproteins mediates antibody-dependent cellular cytotoxicity on HIV-1-infected cells. J Immunol. 2014 Aug 15;193(4):1544-8. (doi: 10.4049/jimmunol.1302108.) [PMID: 25024383, PMCID: PMC4120895] Epub 2014 Jul 14.
Alzhanova D, Hammarlund E, Reed J, Meermeier E, Rawlings S, Ray CA, Edwards DM, Bimber B, Legasse A, Planer S, Sprague J, Axthelm MK, Pickup DJ, Lewinsohn DM, Gold MC, Wong SW, Sacha JB, Slifka MK, Früh K. T cell inactivation by poxviral B22 family proteins increases viral virulence. PLoS Pathog. 2014 May 15;10(5):e1004123. (doi: 10.1371/journal.ppat.1004123.) [PMID: 24832205, PMCID: PMC4022744] eCollection 2014.
Sacha Laboratory Link (click here)