Sacha Laboratory

Welcome to the Sacha Laboratory, located in the Vaccine & Gene Therapy Institute and Oregon National Primate Research Center at the Oregon Health & Science University. We are a dedicated team of scientists working towards ameliorating human suffering by solving the AIDS epidemic and improving clinical care.

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.  The enormous sequence diversity of HIV remains one of the top challenges to be overcome in developing an effective prophylactic vaccine (see illustration below).  My laboratory aims to determine which antigens should be targeted to overcome the formidable obstacle of HIV viral sequence diversity.  Thus, we are actively exploring four distinct, but related areas of immunity to highly variable pathogens such as HIV.

0-10-1 Influenza-Diversity
An illustrative example of the extreme diversity of HIV versus influenza, which demonstrates the need for new vaccine approaches. From Korber et al., British Medical Bulletin, 2001.

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.

An endogenous retrovirus genome is pictured.  These proviruses are present in the germ line DNA of all mammals, accounting for an astounding 8% of the human genome.  Some of the proviruses are still able to produce proteins, raising the possibility that they be targeted by the immune system during pathological processes.


The durable HIV functional cure of Timothy Brown (aka "The Berlin Patient") and the transient HIV remission observed in the Boston Patients indicate that stem cell transplants may be able to deplete HIV reservoirs and control HIV replication. Graft-versus-host disease (GvHD) is a common side effect of stem cell transplants and such immunity may be responsible for the remarkable lack of HIV seen in these transplant recipients. To determine how GvHD impacts HIV, we have established a physiologically relevant model of allogeneic stem cell transplantation and are actively studying GvHD as a means to attack HIV. These studies will also help improve cancer therapy by determining how to maintain the positive effect of graft-versus-tumor immunity while minimizing the unwanted effects of GvHD.

The number of stem cell (bone marrow) transplant procedures increases each year. Our model will also help improve quality of living of patients undergoing stem cell transplants by reducing GvHD while maintianing the protective graft-versus-tumor effect.

Sequence diversity

Viral sequence diversity is the Achilles’ heel of traditional vaccine approaches and poses one of the greatest hurdles to vaccine development.  New, unconventional 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.  An example of one approach is shown below.

An example of an alternate target for vaccination: HIV-induced degradation of the innate antiviral APOBEC protein. (A) HIV infectes a target cell and (B) produces the Vif protein. (C) Vif targets APOBEC to the proteasome for destruction. However, because proteasomal degradation generates CD8+ T cell epitopes, (D) HIV-infected cells are marked by a significant increase in MHC-I bound APOBEC-derived CD8+ T cells. A vaccine targeting this could theoretically defeat the sequence diversity of HIV.


Major histocompatibility complex (MHC) class I alleles are the most diverse loci in the human population. Indeed, over 8,500 MHC-I alleles exist. In contrast, only two HLA-E molecules exist, raising the possibility of a truly universal vaccine, with which every vaccinated individual would mount identical HLA-E restricted CD8+ T cell responses. We are actively investigating the novel characteristics of MHC-E to understand how to mobilize this remarkable immune molecule for vaccines against variable pathogens.

A schematic of the HLA-E molecule. MHC-E is highly monomorphic and expressed in nearly every nucleated cell in the body. Although MHC-E has been traditionally viewed as negative receptor for innate NK cells, we have found that MHC-E also possess a previously underappreciated ability to bind diverse peptide for presentation to CD8+ T cells in adaptive immunity.

Postdoctoral Fellows: Postdoctoral fellows with expertise in immunology and/or virology should submit a copy of their CV to

Graduate Students:  Graduate students are the lifeblood of the laboratory and the future of the field. If you are a current Molecular Microbiology & Immunology graduate student interested in rotating in the Sacha laboratory, please contact

If you are interested in graduate studies at OHSU, we encourage you to apply to the Department of Molecular Microbiology & Immunology.

Undergraduates:  We are currently recruiting motivated, bright young individuals interested in pursuing a career in research or medicine. 

If you attend one of the many Portland area undergraduate institutions please contact to discuss the possibility of joining the laboratory.

If you attend an institution outside the Portland area and are interested in a summer research position, please apply to the ONPRC Undergraduate Summer Fellowship Program.

Research Technician:  We are actively recruiting motivated individuals to work as research technicians. Previous individuals in this role have successfully matriculated into graduate or medical school.

Malouli D, Gilbride RM, Wu HL, Hwang JM, Maier N, Hughes CM, Newhouse D, Morrow D, Ventura AB, Law L, Tisoncik-Go J, Whitmore L, Smith E, Golez I, Chang J, Reed JS, Waytashek C, Weber W, Taher H, Uebelhoer LS, Womack JL, McArdle MR, Gao J, Papen CR, Lifson JD, Burwitz BJ, Axthelm MK, Smedley J, Früh K, Gale M Jr, Picker LJ, Hansen SG, Sacha JB. Cytomegalovirus-vaccine-induced unconventional T cell priming and control of SIV replication is conserved between primate species. Cell Host & Microbe. 2022 Aug 12:S1931-3128(22)00359-6.

Chan M, Tiwary M, Wu HL, Tailor N, Vendramelli R, Audet J, Warner BM, Tierney K, Albietz A, Truong T, Doan K, Bello A, Willman M, Griffin BD, Hanley PW, Lovaglio J, Safronetz D, Strong J, Sacha JB, Kobasa D. Pandemic 1918 Influenza Virus Does Not Cause Lethal Infection in Rhesus or Cynomolgus Macaques. Journal of Virology. 2022 Aug 24;96(16):e0072822. Indicates co-senior authors.

Smedley JV, Bochart RM, Fischer M, Funderburgh H, Kelly V, Crank H, Armantrout K, Shiel O, Robertson-LeVay M, Sternberger N, Schmaling B, Roberts S, Sekiguchi V, Reusz M, Schwartz T, Meyer KA, Webb G, Gilbride RM, Dambrauskas N, Andrade D, Wood M, Labriola C, Axthelm M, Derby N, Varco-Merth B, Fukazawa Y, Hansen S, Sacha JB, Sodora DL, Sather DN. Optimization and use of near infrared imaging to guide lymph node collection in rhesus macaques (Macaca mulatta). Journal of Medical Primatology. 2022 Jul 15.

Biswas S, Rust LN, Wettengel JM, Yusova S, Fischer M, Carson JN, Johnson J, Wei L, Thode T, Kaadige MR, Sharma S, Agbaria M, Bimber BN, Tu T, Protzer U, Ploss A, Smedley JV, Golomb G, Sacha JB, Burwitz BJ. Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity. Nature Communications. 2022 May 30;13(1):2995. Indicates co-senior authors.

Gaylis NB, Ritter A, Kelly SA, Pourhassan NZ, Tiwary M, Sacha JB, Hansen SG, Recknor C, Yang OO. Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome. Clinical Infectious Diseases. 2022 Apr 22:ciac226.

Chang XL, Reed JS, Webb GM, Wu HL, Le J, Bateman KB, Greene JM, Pessoa C, Waytashek C, Weber WC, Hwang J, Fischer M, Moats C, Shiel O, Bochart RM, Crank H, Siess D, Giobbi T, Torgerson J, Agnor R, Gao L, Dhody K, Lalezari JP, Bandar IS, Carnate AM, Pang AS, Corley MJ, Kelly S, Pourhassan N, Smedley J, Bimber BN, Hansen SG, Ndhlovu LC, Sacha JB. Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species. PLoS Pathogens. 2022 Mar 31;18(3):e1010396.

Chang XL, Wu HL, Webb GM, Tiwary M, Hughes C, Reed JS, Hwang J, Waytashek C, Boyle C, Pessoa C, Sylwester AW, Morrow D, Belica K, Fischer M, Kelly S, Pourhassan N, Bochart RM, Smedley J, Recknor CP, Hansen SG, Sacha JB. CCR5 Receptor Occupancy Analysis Reveals Increased Peripheral Blood CCR5+CD4+ T Cells Following Treatment With the Anti-CCR5 Antibody Leronlimab. Frontiers in  Immunology. 2021 Nov 19;12:794638.

Abdulhaqq S, Ventura AB, Reed JS, Bashirova AA, Bateman KB, McDonald E, Wu HL, Greene JM, Schell JB, Morrow D, Wisskirchen K, Martin JN, Deeks SG, Carrington M, Protzer U, Früh K, Hansen SG, Picker LJ, Sacha JB, Bimber BN. Identification and Characterization of Antigen-Specific CD8 + T Cells Using Surface-Trapped TNF-α and Single-Cell Sequencing Journal of Immunology. 2021 Nov 22:ji2100535. Indicates co-senior authors.

Bliss-Moreau E, Amara RR, Buffalo EA, Colman RJ, Embers ME, Morrison JH, Quillen EE, Sacha JB, Roberts CT; National Primate Research Center Consortium Rigor and Reproducibility Working Group. mproving rigor and reproducibility in nonhuman primate research. American Journal of Primatology. 2021 Dec;83(12):e23331.

Wen J, Cheever T, Wang L, Wu D, Reed J, Mascola J, Chen X, Liu C, Pegu A, Sacha JB, Lu Y, Haigwood NL, Chen ISY. Improved delivery of broadly neutralizing antibodies by nanocapsules suppresses SHIV infection in the CNS of infant rhesus macaques. PLoS Pathogens. 2021 Jul 20;17(7):e1009738.

Chang XL, Webb GM, Wu HL, Greene JM, Abdulhaqq S, Bateman KB, Reed JS, Pessoa C, Weber WC, Maier N, Chew GM, Gilbride RM, Gao L, Agnor R, Giobbi T, Torgerson J, Siess D, Burnett N, Fischer M, Shiel O, Moats C, Patterson B, Dhody K, Kelly S, Pourhassan N, Magnani DM, Smedley J, Bimber BN, Haigwood NL, Hansen SG, Brown TR, Ndhlovu LC, Sacha JB. Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission. Nature Communications. 2021 Jun 7;12(1):3343.

Verweij MC, Hansen SG, Iyer R, John N, Malouli D, Morrow D, Scholz I, Womack J, Abdulhaqq S, Gilbride RM, Hughes CM, Ventura AB, Ford JC, Selseth AN, Oswald K, Shoemaker R, Berkemeier B, Bosche WJ, Hull M, Shao J, Sacha JB, Axthelm MK, Edlefsen PT, Lifson JD, Picker LJ, Früh K. Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy. Science. 2021 Apr 30;372(6541):eabe9233.

Malouli D, Hansen SG, Hancock MH, Hughes CM, Ford JC, Gilbride RM, Ventura AB, Morrow D, Randall KT, Taher H, Uebelhoer LS, McArdle MR, Papen CR, Espinosa Trethewy R, Oswald K, Shoemaker R, Berkemeier B, Bosche WJ, Hull M, Greene JM, Axthelm MK, Shao J, Edlefsen PT, Grey F, Nelson JA, Lifson JD, Streblow D, Sacha JB, Früh K, Picker LJ. Cytomegaloviral determinants of CD8 + T cell programming and RhCMV/SIV vaccine efficacy. Science Immunology. 2021 Mar 25;6(57):eabg5413.

Yang H, Rei M, Brackenridge S, Brenna E, Sun H, Abdulhaqq S, Liu MKP, Ma W, Kurupati P, Xu X, Cerundolo V, Jenkins E, Davis SJ, Sacha JB, Früh K, Picker LJ, Borrow P, Gillespie GM, McMichael AJ.  HLA-E-restricted, Gag-specific CD8 + T cells can suppress HIV-1 infection, offering vaccine opportunities.  Science Immunology. 2021 Mar 25;6(57):eabg1703.

Malherbe DC, Vang L, Mendy J, Barnette PT, Spencer DA, Reed J, Kareko BW, Sather DN, Pandey S, Wibmer CK, Robins H, Fuller DH, Park B, Lakhashe SK, Wilson JM, Axthelm MK, Ruprecht RM, Moore PL, Sacha JB, Hessell AJ, Alexander J, Haigwood NL. Modified Adenovirus Prime-Protein Boost Clade C HIV Vaccine Strategy Results in Reduced Viral DNA in Blood and Tissues Following Tier 2 SHIV Challenge Frontiers in Immunology. 2021 Feb 15;11:626464.

Agresti N, Lalezari JP, Amodeo PP, Mody K, Mosher SF, Seethamraju H, Kelly SA, Pourhassan NZ, Sudduth CD, Bovinet C, ElSharkawi AE, Patterson BK, Stephen R, Sacha JB, Wu HL, Gross SA, Dhody K. Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with Leronlimab. Journal of Translational Autoimmunity. 2021;4:100083.

Corley MJ, Pang APS, Dody K, Mudd PA, Patterson BK, Seethamraju H, Bram Y, Peluso MJ, Torres L, Iyer NS, Premeaux TA, Yeung ST, Chandar V, Borczuk A, Schwartz RE, Henrich TJ, Deeks SG, Sacha JB, Ndhlovu LC. Genome-wide DNA methylation profiling of peripheral blood reveals an epigenetic signature associated with severe COVID-19. Journal of Leukocyte Biology. 2021 Jan 19.

Hope TJ, Klatt NR, Sacha JB, Cannon PM. Timothy Ray Brown: The Serendipitous Hero of HIV Cure Research. AIDS Research and Human Retroviruses. 2020 Nov;36(11):883-885.

Patterson BK, Seethamraju H, Dhody K, Corley MJ, Kazempour K, Lalezari J, Pang APS, Sugai C, Mahyari E, Francisco EB, Pise A, Rodrigues H, Wu HL, Webb GM, Park BS, Kelly S, Pourhassan N, Lelic A, Kdouh L, Herrera M, Hall E, Bimber BN, Plassmeyer M, Gupta R, Alpan O, O'Halloran JA, Mudd PA, Akalin E, Ndhlovu LC, Sacha JB. CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14. International Journal for Infectious Diseases. 2020 Nov 10;103:25-32.

Yang B, Fulcher JA, Ahn J, Berro M, Goodman-Meza D, Dhody K, Sacha JB, Naeim A, Yang OO. Clinical Characteristics and Outcomes of COVID-19 Patients Receiving Compassionate Use Leronlimab. Clinical  Infectious Diseases. 2020 Oct 20:ciaa1583.

Wu HL, Greene JM, Swanson T, Shriver-Munsch C, Armantrout K, Weber WC, Bateman KB, Maier NM, Northrup M, Legasse AW, Moats C, Axthelm MK, Smedley J, Maziarz RT, Martin LD, Hobbs T, Burwitz BJ, Sacha JB. Terumo spectra optia leukapheresis of cynomolgus macaques for hematopoietic stem cell and T cell collection. Journal Clinical Apheresis. 2020 Sep 17.

Rosen BC, Pedreño-Lopez N, Ricciardi MJ, Reed JS, Sacha JB, Rakasz EG, Watkins DI. Rhesus Cytomegalovirus-Specific CD8 + Cytotoxic T Lymphocytes Do Not Become Functionally Exhausted in Chronic SIVmac239 Infection. Frontiers in Immunology. 2020 Aug 12;11:1960.

Malherbe DC, Wibmer CK, Nonyane M, Reed J, Sather DN, Spencer DA, Schuman JT, Guo B, Pandey S, Robins H, Park B, Fuller DH, Sacha JB, Moore PL, Hessell AJ, Haigwood NL. Rapid Induction of Multifunctional Antibodies in Rabbits and Macaques by Clade C HIV-1 CAP257 Envelopes Circulating During Epitope-Specific Neutralization Breadth Development. Frontiers in Immunology. 2020 Jun 2;11:984.

Webb GM, Molden J, Busman-Sahay K, Abdulhaqq S, Wu HL, Weber WC, Bateman KB, Reed JS, Northrup M, Maier N, Tanaka S, Gao L, Davey B, Carpenter BL, Axthelm MK, Stanton JJ, Smedley J, Greene JM, Safrit JT, Estes JD, Skinner PJ, Sacha JB. The human IL-15 superagonist N-803 promotes migration of virus-specific CD8+ T and NK cells to B cell follicles but does not reverse latency in ART-suppressed, SHIV-infected macaques. PLoS Pathogens. 2020 Mar 12;16(3):e1008339.

Burwitz BJ, Hansen SG, Hashiguchi P, Gilbride R, Picker LJ, Früh K, Sacha JB.  MHC-E-restricted CD8+ T cells Recognize HBV-infected human hepatocytes. Journal of Immunology. 2020 Apr 15;204(8):2169-2176.

Steinbach RJ, Haese NN, Smith JL, Colgin LMA, MacAllister RP, Greene JM, Parkins CJ, Kempton JB, Porsov E, Wang X, Renner LM, McGill TJ, Dozier BL, Kreklywich CN, Andoh TF, Grafe MR, Pecoraro HL, Hodge T, Friedman RM, Houser LA, Morgan TK, Stenzel P, Lindner JR, Schelonka RL, Sacha JB, Roberts VHJ, Neuringer M, Brigande JV, Kroenke CD, Frias AE, Lewis AD, Kelleher MA, Hirsch AJ, Streblow DN. A neonatal nonhuman primate model of gestational Zika virus infection with evidence of microencephaly, seizures and cardiomyopathy. PLoS One. 2020 Jan 14;15(1).

Wu HL, Weber WC, Shriver-Munsch C, Swanson T, Northrup M, Price H, Armantrout K, Robertson-LeVay M, Reed JS, Bateman KB, Mahyari E, Thomas A, Junell SL, Hobbs TR, Martin LD, MacAllister R, Bimber BN, Slifka MK, Legasse AW, Moats C, Axthelm MK, Smedley J, Lewis AD, Colgin L, Meyers G, Maziarz RT, Burwitz BJ, Stanton JJ, Sacha JB. Viral opportunistic infections in Mauritian cynomolgus macaques undergoing allogeneic stem cell transplantation mirror human transplant infectious disease complications. Xenotransplantation. 2020 Jan 13:e12578

Shapiro MB, Cheever T, Malherbe DC, Pandey S, Reed J, Yang ES, Wang K, Pegu A, Chen X, Siess D, Burke D, Henderson H, Lewinsohn R, Fischer M, Stanton JJ, Axthelm MK, Kahl C, Park B, Lewis AD, Sacha JB, Mascola JR, Hessell AJ, Haigwood NL. Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity. Nature Communications. 2020 Jan 7;11(1):70

Hansen SG, Marshall EE, Malouli D, Ventura AB, Hughes CM, Ainslie E, Ford JC, Morrow D, Gilbride RM, Bae JY, Legasse AW, Oswald K, Shoemaker R, Berkemeier B, Bosche WJ, Hull M, Womack J, Shao J, Edlefsen PT, Reed JS, Burwitz BJ, Sacha JB, Axthelm MK, Früh K, Lifson JD, Picker LJ. A live-attenuated RhCMV/SIV vaccine shows long-term efficacy against heterologous SIV challenge. Science Translational Medicine. 2019 Jul 17;11(501).

Abdulhaqq SA, Wu H, Schell JB, Hammond KB, Reed JS, Legasse AW, Axthelm MK, Park BS, Asokan A, Früh K, Hansen SG, Picker LJ, Sacha JB. Vaccine-Mediated Inhibition of the Transporter Associated with Antigen Processing Is Insufficient To Induce Major Histocompatibility Complex E-Restricted CD8+ T Cells in Nonhuman Primates. Journal of Virology. 2019 Sep 12;93(19)

Walters LC, Harlos K, Brackenridge S, Rozbesky D, Barrett JR, Jain V, Walter TS, O'Callaghan CA, Borrow P, Toebes M, Hansen SG, Sacha JB, Abdulhaqq S, Greene JM, Früh K, Marshall E, Picker LJ, Jones EY, McMichael AJ, Gillespie GM. Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding. Nature Communications. 2018 Aug 7;9(1):3137.

Webb GM, Li S, Mwakalundwa G, Folkvord JM, Greene JM, Reed JS, Stanton JJ, Legasse AW, Hobbs T, Martin LD, Park BS, Whitney JB, Jeng EK, Wong HC, Nixon DF, Jones RB, Connick E, Skinner PJ, Sacha JB. The Human IL-15 Superagonist ALT-803 Directs SIV-specific CD8+ T cells into B Cell Follicles. Blood Advances. 2018 Jan 23;2(2):76-84.

Wu HL, Wiseman RW, Hughes CM, Webb GM, Abdulhaq SA, Hammond KB, Reed JS, Gao L, Burwitz BJ, Greene JM, Ferrer F, Legasse AW, Axthelm MK, Park BS, Breckenridge S, Maness NJ, McMichael AJ, Picker LJ, O'Connor DH, Hansen SG, Sacha JB. The Role of MHC-E in T Cell Immunity is Conserved across Primate Species. Journal of Immunology. 2018 Jan 1;200(1):49-60.

Burwitz BJ, Wu HL, Abdulhaqq S, Shriver-Munsch C, Swanson T, Legasse AW, Hammond KB, Junell SL, Reed J,Bimber BN, Greene JM, Webb GM, Northrup M, Laub W, Kievet P, MacAllister R, Axthelm MK, Ducore R, Lewis A, Colgin LMA, Hobbs T, Martin LD, Thomas CR, Panoskaltsis-Mortari A, Meyers G, Stanton JJ, Maziarz RT, Sacha JB. Allogeneic Stem Cell Transplantation in fully MHC-matched Mauritian Cynomolgus Macaques Recapitulates Diverse Human Clinical Outcomes. Nature Communications. 2017 Nov 10;8(1):1418.

Burwitz BJ, Wettengel JM, Mück-Häusl M, Hammond KB, Ringelhan M, Reed JS, Norris R, Park B, Moller-Tank S, Esser K, Greene JM, Wu HL, Abdulhaqq S, Webb G, Sutton WF, Legasse AW,Asokan A, Haigwood NL, Prozter U, Sacha JB. Hepatocytic Expression of Human Sodium Taurocholate Cotransporting Polypeptide (NTCP) Enables Hepatitis B Virus Infection of Macques. Nature Communications. 2017 Dec 15;8(1):2146.

de Mulder M, SenGupta D, Deeks SG, Martin JN, Pilcher CD, Hecht FM, Sacha JB, Nixon DF, and Michaud HA. Anti-HERV-K (HML-2) capsid antibody responses in HIV elite controllers. Retrovirology. 2017 August22;14(1):41.

Ericsen AJ, Lauck M, Mohns MS, DiNapoli SR, Mutschler JP, Greene JM, Weinfurter JT, Crosno KA, Peterson EJ, Wiseman RW, Burwitz BJ, Sacha JB, Friedrich TC, Brenchley JM, O'Connor DH. Hyperacute microbial translocation during AIDS virus infection. PLos Pathogens. 2016 Dec7;12(12):e1006048.

Burwitz BJ, Malouli D, Bimber BN, Reed JS, Ventura AB,Hancock MH, Uebelhoer LS, Bhusari A, Hammond KB, Espinosa Trethewy RG, Klug A,Legasse AW, Axthelm MK, Nelson JA, Park BS, Streblow DN, Hansen SG, Picker LJ,Früh K, Sacha JB. Cross-SpeciesRhesus Cytomegalovirus Infection of Cynomolgus Macaques. PLoS Pathogens.2016 Nov 9;12(11):e1006014.

Greene JM, Dash P, Roy S, McMurtrey C, Awad W, Reed JS,Hammond KB, Abdulhaqq S, Wu HL, Burwitz BJ, Roth BF, Morrow DW, Ford JC, Xu G,Bae JY, Crank H, Legasse AW, Dang TH, Greenaway HY, Kurniawan M, Gold MC,Harriff MJ, Lewinsohn DA, Park BS, Axthelm MK, Stanton JJ, Hansen SG, PickerLJ, Venturi V, Hildebrand W, Thomas PG, Lewinsohn DM, Adams EJ, Sacha JB. MR1-restrictedmucosal-associated invariant T (MAIT) cells respond to mycobacterialvaccination and infection in nonhuman primates. Mucosal Immunology.2016 Oct 19.

Sacha JB, Ndhlovu LC. Strategies to target non-T cell HIVreservoirs. Current Opinions in HIVAIDS. 2016 Jul;11(4):376-82.

Hessell AJ, Jaworski JP, Epson E, Matsuda K, Pandey S, KahlC, Reed J, Sutton WF, Hammond KB, Legasse A, Planer S, Stanton J, Pegu A, ChenX, Axthelm M, Lewis A, Hirsch VM, Graham BS, Mascola JR, Sacha JB, Haigwood NL.Early short-term treatment with neutralizing human monoclonal antibodiesintercepts viral reservoir establishment in SHIV-exposed newborn macaques. Nature Medicine. 2016Apr;22(4):362-8.

Hansen SG, Wu HL, Burwitz BJ, Hughes CM, Hammond KB, VenturaAB, Reed JS, Gilbride RM, Ainslie E, Morrow DW, Ford JC, Selseth AN, Pathak R,Malouli D, Legasse AW, Axthelm MK, Nelson JA, Gillespie GM, Walters LC,Brackenridge S, Sharpe HR, Lopez CA, Früh K, Korber BT, McMichael AJ,Gnanakaran S, Sacha JB†, Picker LJ†. Broadlytargeted CD8+ T cell responses restricted by major histocompatibility complex-E. Science. 2016 Feb12;351(6274):714-20. †Indicates co-senior authors.

Wu HL, Leon EJ, Wallace LT, Nimiyongskul FA, Buechler MB,Newman LP, Castrovinci PA, Johnson RP, Gifford RJ, Jones RB, Sacha JB.Identification and spontaneous immune targeting of an endogenous retrovirus Kenvelope protein in the indian rhesus macaque model of human disease. Retrovirology. 2016 Jan15;13:6.

Chew GM, Fujita T, Webb GM, Burwitz BJ, Wu HL, Reed JS,Hammond KB, Clayton KL, Ishii N, Abdel-MohsenM, Liegler T, Mitchell BI, HechtFM, Ostrowski M, Shikuma CM, Hansen SG, Maurer M, Korman AJ, Deeks SG, Sacha JB†,Ndhlovu LC†. TIGIT marks exhausted T cells, correlates with diseaseprogression, and serves as a target for immune restoration in HIV and SIVInfection. PLoS Pathogens. 2016 Jan 7;12(1):e1005349. †Indicatesco-senior authors.

Rhode PR, Egan JO, Xu W, Hong H, Webb GM, Chen X, Liu B, ZhuX, Wen J, You L, Kong L, Edwards AC, Han K, Shi S, Alter S, Sacha JB, Jeng EK,Cai W, Wong HC. Comparison of the Superagonist Complex, ALT-803, to IL15 asCancer Immunotherapeutics in Animal Models. Cancer Immunology Research. 4(1) January 2016.

Fujita T, Burwitz BJ, Chew GM, Reed JS, Clayton K, Ostrowski M, Ishii N, Sacha JB†, and Ndhlovu LC†. Expansion of dysfunctional Tim-3 expressing effector memory CD8+ T cells during SIV infection of rhesus macaques. Journal of Immunology, 2014 Dec 1;193(11):5576-83. †Indicates co-senior authors.

Burwitz BJ, Reed JS, Hammond KB, Ericson A, Richter Y, Golomb G, and Sacha JB. Liposomal alendronate depletion of monocytes and macrophages in the nonhuman primate model of human disease. Journal of Leukocyte Biology, 2014 Sep;96(3):491-501.

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. Journal of Immunology, 2014 Aug 15;193(4):1544-8.

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, Frueh K. T cell inactivation by poxviral B22 family proteins increases viral virulence. PLoS Pathog. 2014 May 15;10(5):e1004123. PMCID: PMC4022744

Burwitz BJ, Wu HL, Reed JS, Newman LP, Bimber BN, Nimiyongskul FA, Leon EJ, Maness NJ, Friedrich TC, Masaru Yokoyama, Hinonori Sato, Tetsuro Matano, O'Connor DH, and Sacha JB. Tertiary mutations stabilize

CD8+ T lymphocyte escape-associated compensatory mutations following transmission of simian immunodeficiency virus. Journal of Virology, 2014 Mar;88(6):3598-604. PMCID: PMC3957937.

Michaud HA, de Mulder M, SenGupta D, Deeks SG, Martin JN, Pilcher CD, Hecht FM, Sacha JB, Nixon DF. Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection. Retrovirology. 2014 Jan 28;11:10.

Sheppard NC, Jones RB, Burwitz BJ, Nimityongskul FA, Newman LP, Buechler MB, Reed JS, Piaskowski SM, Weisgrau KL, Castrovinci PA, Wilson NA, Ostrowski MA, Park B, Nixon DF, Rakasz EG, Sacha JB. Vaccination against endogenous retrotransposable element consensus sequences does not protect rhesus macaques from SIVsmE660 infection and replication. PLoS One. 2014 Mar 20;9(3):e92012.

Hansen SG, Piatak M, Ventura AB, Hughes CM, Gilbride RM, Ford JC, Burwitz BJ, Planer SL, TurnerJM, Legasse AW, Axthelm MK, Edlefsen PT, Nelson JA, Fr¸h K, Estes JD, Sacha JB, Lifson JD, and Picker LJ. Immune clearance of highly pathogenic SIV infection. Nature. 2013 Oct 3;502(7469):100-4.

Jaworski JP, Kobie J, Brower Z, Malherbe DC, Landucci G, Sutton WF, Guo B, Reed JS, Leon EJ, Engelmann F, Zheng B, Legasse A, Park B, Dickerson M, Lewis AD, Colgin LM, Axthelm M, Messaoudi I,Sacha JB, Burton DR, Forthal DN, Hessell AJ, Haigwood NL. Neutralizing polyclonal IgG present during acute infection prevents rapid disease onset in simian-human immunodeficiency virus SHIVSF162P3-infected infant rhesus macaques. Journal of Virology. 2013 Oct;87(19):10447-59.

Hansen SG, Sacha JB, Hughes CM, Ford JC, Burwitz BJ, Scholz I, Gilbride RM, Gilliam AN, Lewis MS, Ventura AB, Xu G, Malouli D, Richards R, Whizin N, Reed JS, Hammond KB, Fischer M, Turner JM, Legasse AW, Axthelm MK, Edlefsen PT, Nelson JA, Lifson JD, Frueh K, and Picker LJ. Cytomegalovirus Vectors Violate CD8+ T Cell Epitope Recognition Paradigms. Science. 2013 May 24;340(6135):1237874.

Champiat S, Garrison KE, Raposo RA, Burwitz BJ, Reed J, Tandon R, York VA, Newman LP, Nimityongskul FA, Wilson NA, Almeida RR, Martin JN, Deeks SG, Rosenberg MG, Wiznia AA, Spotts GE, Pilcher CD, Hecht FM, Ostrowski MA, Sacha JB†, Nixon DF†. T Cells Target APOBEC3 Proteins in HIV-1-infected Humans and SIV- infected Indian Rhesus Macaques. Journal of Virology. 2013 Jun;87(11):6073-80. †Indicates co-senior authors.

1Kloverpris HN, Payne RP, Sacha JB, Rasaiyaah JT, Chen F, Takiguchi M, Yang OO, Towers GJ, Goulder P, Prado JG. Early antigen presentation of protective HIV-1 KF11Gag and KK10Gag epitopes from incoming viral particles facilitates rapid recognition of infected cells by specific CD8+ T cells. Journal of Virology. 2013 Mar; 87(5):2628-38.

Jones RB, Garrison KE, Mujib S, Mihajlovic V, Aidarus N, Hunter DV, Martin E, John VM, Zhan W, Faruk NF, Gyenes G, Sheppard NC, Priumboom-Brees IM, Goodwin DA, Chen L, Rieger M, Muscat-King S, Loudon PT, Stanley C, Holditch SJ, Wong JC, Clayton K, Duan E, Song H, Xu Y, SenGupta D, Tandon R, Sacha JB, Brockman MA, Benko E, Kovacs C, Nixon DF, Ostrowski MA. HERV-K(HML-2)-specific CD8+ T cells recognize and eliminate cells infected with globally diverse HIV-1, HIV-2, and SIV primary isolates. Journal of Clinical Investigation. 2012 Dec 3;122(12):4473-89

Burwitz BJ, Giraldo-Vela JP, Reed J, Newman LP, Bean AT, Nimityongskul FA, Castrovinci PA, Maness NJ, Leon EJ, Rudersdorf R, Sacha JB. CD8+ and CD4+ cytotoxic T cell escape mutations precede breakthrough SIVmac239 viremia in an elite controller. Retrovirology. 2012 Nov 6;9:91. PMCID: 3496649

Sacha JB, Kim IJ, Chen L, Ullah JH, Goodwin DA, Simmons HA, Schenkman DI, von Pelchrzim F, Gifford RJ, Nimityongskul FA, Newman LP, Wildeboer S, Lappin PB, Hammond D, Castrovinci P, Piaskowski SM, Reed JS, Beheler KA, Tharmanathan T, Zhang N, Muscat-King S, Rieger M, Fernandes C, Rumpel K, Gardner JP 2nd, Gebhard DH, Janies J, Shoieb A, Pierce BG, Trajkovic D, Rakasz E, Rong S, McCluskie M, Christy C, Merson JR, Jones RB, Nixon DF, Ostrowski MA, Loudon PT, Pruimboom-Brees IM, Sheppard NC. Vaccination with Cancer- and HIV Infection-associated Endogenous Retrotransposable Elements is Safe and Immunogenic. Journal of Immunology. 2012 Aug 1;189(3):1467-79. PMCID: PMC3401319

1Vojnov L, Martins MA, Beat AT, Veloso de Santana MG, Sacha JB, Wilson NA, Bonaldo MC, Galler R, Stevenson M, Watkins DI. The majority of freshly sorted simian immunodeficiency virus (SIV)-specific CD8+ T cells cannot suppress viral replication in SIV-infected macrophages. Journal of Virology. 2012 Apr;86(8):4682-7. PMCID: PMC3318662

Burwitz BJ†, Sacha JB†, Reed J, Newman LP, Norante FA, Bimber BN, Wilson NA, Watkins DI, and O'Connor DH (2011). Pyrosequencing reveals restricted patterns of CD8+ T cell escape associated compensatory mutations in SIV. Journal of Virology. Dec;85(24):13088-96. †Indicates co-first authors.

Reynolds MR, Sacha JB, Weiler AM, Borchardt GJ, Glidden CE, Sheppard NC, Norante FA, Castrovinci PA, Harris JJ, Robertson HT, Friedrich TC, McDermott AB, Wilson NA, Allison DB, Koff WC, Johnson WE, Watkins DI (2011). TRIM5a genotype of rhesus macaques affects acquisition of SIVsmE660 infection after repeated limiting-dose intrarectal challenge. Journal of Virology. 85(18): 9637-40.

Vojnov L, Bean AT, Peterson EJ, Chiuchiolo MJ, Sacha JB, Denes FS, Sandor M, Fuller DH, Fuller JT, Parks CL, McDermott AB, Wilson NA, Watkins DI (2011). DNA/Ad5 vaccination with SIV epitopes induced epitope- specific CD4(+) T cells, but few subdominant epitope-specific CD8(+) T cells. Vaccine. 2011 Oct 6;29(43): 7483-90.

Sacha JB, Buechler MB, Newman LP, Reed J, Wallace LT, Wilson NA, and Watkins DI. (2010) SIV-specific CD8+ T cells recognize Vpr- and Rev-derived epitopes early after infection. Journal of Virology. 84(20):10543-57.

Payne RP, Kloverpris H, Sacha JB, Buus S, Sims S, Hickling S, Riddell L, Chen F, Luzzi G, Edwards A, Prado JG, Goulder PJ (2010). Efficacious antiviral activity of HLA-B*2705-restricted CD8+ T cells is associated with early recognition of HIV-infected cells and not to a superior functional CD8+ T cell profile.Journal of Virology. 84(20) 10907-12.

Bonaldo MC, Martins MA, Rudersdorf R, Mudd PM, Sacha JB, Piaskowski SM, da Costa Neves PC, Veloso de Santana MG, Vojnov L, Capuano III S, Rakasz EG, Wilson NA, Fulkerson J, Sadoff JC, Watkins DI, Galler R (2010). Recombinant yellow fever vaccine virus 17D expressing SIVmac239 Gag induces SIV-specific CD8+ T cell responses in rhesus macaques. Journal of Virology. 84(7): 3699 - 3706.

Maness NJ, Wilson NA, Reed J, Piaskowski SM, Sacha JB, Walsh AD, Thoryk E, Heidecker GJ, Citron MP, Liang X, Bett AJ, Casimiro DR, and Watkins DI (2010). Robust vaccine-induced CD8+ T lymphocyte response against an out of frame epitope. Journal of Immunology. 84: 67-72

Sacha JB and Watkins DI (2010). Synchronous infection of SIV and HIV in vitro for virology, immunology, and vaccine-related studies. Nature Protocols. Feb;5(2):239-46

Vojnov L, Reed JS, Weisgrau KL, Piaskowski SM, Rakasz EG, Loffredo JT, Sacha JB, Wilson NA, Johnson RP, Watkins DI (2010). Effective SIV-specific CD8+ T cells lack an easily detectable, shared characteristic.Journal of Virology. 84: 753-764.

Maness NJ, Sacha JB, Piaskowski SM, Weisgrau KL, Rakasz EG, May GE, Buechler MB, Wilson NA, Watkins DI (2009). Novel translation products from the SIVmac239 Env encoding mRNA contain both Rev and cryptic T cell epitopes. Journal of Virology. 83: 10280-10285.

Sacha JB, Giraldo-Vela JP, Buechler MB, Martins MA, Maness NJ, Chung C, Wallace LT, LeÛn EJ, Friedrich TC, Wilson NA, Hiraoka A, Watkins DI (2009). Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. Proceedings of the National Academy of Sciences of the USA. 106:9791-6.

Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, Rood JE, Berkley AM, Sacha JB, Cogliano-Shutta NA, Lloyd M, Roby G, Kwan R, McLaughlin M, Stallings S, Rehm C, O'Shea MA, Mican J, Packard BZ, Komoriya A, Palmer S, Wiegand AP, Maldarelli F, Coffin JM, Mellors JW, Hallahan CW, Follman DA, Connors M (2008). Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity. 29(6):1009-21

Sacha JB, Reynolds MR, Buechler MB, Chung C, Jonas AK, Wallace LT, Weiler AM, Lee W, Piaskowski SM, Soma T, Friedrich TC, Wilson NA, Watkins DI (2008). Differential antigen presentation kinetics of CD8+ T cell epitopes derived from the same viral protein. Journal of Virology. 82:9293-8.

Sacha JB, Chung C, Reed J, Jonas AK, Bean AT, Spencer SP, Lee W, Vojnov L, Rudersdorf R, Friedrich TC, Wilson NA, Lifson JD, Watkins DI (2007). Pol-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells prior to nef-mediated major histocompatibility complex class I downregulation. Journal of Virology 81:11703-12.

Sacha JB, Chung C, Rakasz EG, Spencer SP, Jonas AK, Bean AT, Lee W, Burwitz B, Stephany J, Loffredo JT, Allison DB, Adnan A, Hoji A, Wilson N, Friedrich TC, Lifson JD, Yang OO, Watkins DI (2007). Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and protein expression.Journal of Immunology. 178:2746-54.

Tewari KV†, Sacha J†, Gao X, and Suresh M (2004). Effect of chronic viral Infection on epitope selection, cytokine production, and surface phenotype of CD8+ T cells and the role of IFN-γ receptor in immune regulation. Journal of Immunology. 172: 1491 – 1500. †Indicates co-first authors.

Recent News

  • The Sacha Laboratory published a manuscript in Cell Host & Microbe on defining the cross species requirements of CMV vaccine vector priming of unconventionally MHC-restricted CD8+ T cells.

  • Joseph Hwang gave an invited seminar at the 39th Annual Symposium on NHP Models for AIDS on a CMV based vaccine for influenza. (And did a great job, well done Joseph!)

  • Dr. Sacha gave an invited seminar on a new approach for universal influenza vaccines at the Options for the Control of Influenza Symposium in Belfast, Ireland.

  • The Sacha Laboratory receives an NIH R01 to generate one-time gene therapy injection to treat HIV for life.

  • The Sacha Laboratory published a manuscript in Nature Communications describing the achievement of chronic HBV infection of rhesus macaques.