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profileRoger Keith Reeves, Ph.D.

TitleAssociate Professor of Medicine
InstitutionBeth Israel Deaconess Medical Center
DepartmentMedicine
AddressBeth Israel Deaconess Medical Center
CLS Rm 1036
330 Brookline Ave
Boston MA 02215
Phone508/786-1429
Fax508/624-8172
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Available: 07/27/17, Expires: 08/01/18

NK cells have evolved multiple innate mechanisms to eliminate tumor and virus-infected cells and can also participate in the adaptive immune response by serving as effector cells for antibody-dependent cell-mediated cytotoxicity. NK cells bind antibodies via CD16, also called FcRIII, and traditionally utilize an adaptor molecule gamma-chain for activating downstream signaling pathways after engaging Fc regions of multiple immune-complex associated antibodies. Identification of ‘memory’ and ‘memory-like’ NK cells in mice, primates and humans has garnered an intense interest in understanding mechanisms underlying the development and function of these novel cell types. Recent relevant discoveries suggest that after losing expression of the Fc receptor associated gamma-chain signaling, ‘memory’ NK cells can acquire adaptive-like features in response to viral infections such as HIV or CMV. Preliminary evidence from our laboratory has identified that reduced gamma-chain expression results in switching to alternate signaling pathways for cytotoxic functions that may be more robust. Interestingly, ongoing CMV infection is a necessary co-factor that primes alternate signaling through other adaptor molecules such as CD3zeta, but both traditional and alternate signaling can be disrupted by HIV and SIV infections. A project in the Reeves laboratory would more specifically define alternate signaling pathways in cytotoxic memory and memory-like NK cells and how they may be modulated by CMV and HIV infections. The student would employ cutting edge technologies including phospho-flow cytometry, up to 18-color multiparametric flow cytometry, and in situ hybridization. Given the depth of the techniques used, a background which includes immunology, virology, and/or molecular biology would be helpful.


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The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
R01AI120828     (REEVES, ROGER KEITH)Jul 25, 2017 - Jun 30, 2021
NIH/NIAID
Antigen-Specific NK Cell Memory Against SIV and HIV Vaccines
Role: Principal Investigator

R01DE026327     (REEVES, ROGER KEITH)Aug 1, 2016 - May 31, 2021
NIH/NIDCR
Microbial and innate immune mechanisms of oral inflammation during SIV infection
Role: Principal Investigator

P01AI120756     (TOMARAS, GEORGIA DORIS)May 1, 2016 - Apr 30, 2021
NIH
Bridging Antibody Fc-mediated Antiviral Functions Across Humans and Non-human Primates
Role: Principal Investigator - Project 3

UM1AI124377     (BAROUCH, DAN H.)May 1, 2016 - Apr 30, 2021
NIH/NIAID
Consortia for Innovative AIDS Research in Nonhuman Primates
Role: Co-Investigator

R01DE026014     (REEVES, ROGER KEITH)Apr 1, 2016 - Jan 31, 2021
NIH/NIDCR
Mechanisms of innate modulation of SIV reservoirs and opportunistic disease in the oral cavity
Role: Principal Investigator
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eagle-i@hms.harvard.edu.
CVVR Flow Cytometry Core (BIDMC) - Core services (4) and Instruments (3)

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Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Paust S, Blish CA, Reeves RK. Redefining Memory: Building the Case for Adaptive NK cells. J Virol. 2017 Aug 09. PMID: 28794018.
    View in: PubMed
  2. Schafer JL, Müller-Trutwin MC, Reeves RK. NK cell exhaustion: bad news for chronic disease? Oncotarget. 2015 Sep 08; 6(26):21797-8. PMID: 26392410; PMCID: PMC4673125.
  3. Reeves RK, Burgener A, Klatt NR. Targeting the gastrointestinal tract to develop novel therapies for HIV. Clin Pharmacol Ther. 2015 Oct; 98(4):381-6. PMID: 26179624.
    View in: PubMed
  4. Evans TI, Li H, Schafer JL, Klatt NR, Hao XP, Traslavina RP, Estes JD, Brenchley JM, Reeves RK. SIV-induced Translocation of Bacterial Products in the Liver Mobilizes Myeloid Dendritic and Natural Killer Cells Associated With Liver Damage. J Infect Dis. 2016 Feb 01; 213(3):361-9. PMID: 26238685; PMCID: PMC4704667 [Available on 02/01/17].
  5. Reeves RK, Li H, Jost S, Blass E, Li H, Schafer JL, Varner V, Manickam C, Eslamizar L, Altfeld M, von Andrian UH, Barouch DH. Antigen-specific NK cell memory in rhesus macaques. Nat Immunol. 2015 Sep; 16(9):927-32. PMID: 26193080; PMCID: PMC4545390.
  6. Schafer JL, Li H, Evans TI, Estes JD, Reeves RK. Accumulation of Cytotoxic CD16+ NK Cells in Simian Immunodeficiency Virus-Infected Lymph Nodes Associated with In Situ Differentiation and Functional Anergy. J Virol. 2015 Jul; 89(13):6887-94. PMID: 25903330; PMCID: PMC4468491 [Available on 01/01/16].
  7. Billingsley JM, Rajakumar PA, Connole MA, Salisch NC, Adnan S, Kuzmichev YV, Hong HS, Reeves RK, Kang HJ, Li W, Li Q, Haase AT, Johnson RP. Characterization of CD8+ T cell differentiation following SIV?nef vaccination by transcription factor expression profiling. PLoS Pathog. 2015 Mar; 11(3):e1004740. PMID: 25768938; PMCID: PMC4358830.
  8. Adnan S, Colantonio AD, Yu Y, Gillis J, Wong FE, Becker EA, Piatak M, Reeves RK, Lifson JD, O'Connor SL, Johnson RP. CD8 T cell response maturation defined by anentropic specificity and repertoire depth correlates with SIV?nef-induced protection. PLoS Pathog. 2015 Feb; 11(2):e1004633. PMID: 25688559; PMCID: PMC4334552.
  9. Li H, Richert-Spuhler LE, Evans TI, Gillis J, Connole M, Estes JD, Keele BF, Klatt NR, Reeves RK. Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection. PLoS Pathog. 2014 Dec; 10(12):e1004551. PMID: 25503264; PMCID: PMC4263758.
  10. Li H, Evans TI, Gillis J, Connole M, Reeves RK. Bone marrow-imprinted gut-homing of plasmacytoid dendritic cells (pDCs) in acute simian immunodeficiency virus infection results in massive accumulation of hyperfunctional CD4+ pDCs in the mucosae. J Infect Dis. 2015 Jun 01; 211(11):1717-25. PMID: 25489000.
    View in: PubMed
  11. Manickam C, Reeves RK. Modeling HCV disease in animals: virology, immunology and pathogenesis of HCV and GBV-B infections. Front Microbiol. 2014; 5:690. PMID: 25538700; PMCID: PMC4259104.
  12. Reeves RK, Kang G, Li H, Li Q. Depletion of lamina propria innate lymphoid cells in simian immunodeficiency virus infection. AIDS Res Hum Retroviruses. 2014 Dec; 30(12):1160-1. PMID: 25469593.
    View in: PubMed
  13. Li H, Goepfert P, Reeves RK. Short communication: Plasmacytoid dendritic cells from HIV-1 Elite Controllers maintain a gut-homing phenotype associated with immune activation. AIDS Res Hum Retroviruses. 2014 Dec; 30(12):1213-5. PMID: 25387330.
    View in: PubMed
  14. George MD, Hu W, Billingsley JM, Reeves RK, Sankaran-Walters S, Johnson RP, Dandekar S. Transcriptional profiling of peripheral CD8+T cell responses to SIV?nef and SIVmac251 challenge reveals a link between protective immunity and induction of systemic immunoregulatory mechanisms. Virology. 2014 Nov; 468-470:581-91. PMID: 25282469; PMCID: PMC4252368.
  15. Li H, Evans TI, Connole M, Gillis J, Wong FE, Yu Y, Reeves RK. Acute SIV Infection Rapidly Depletes CD4(+) pDCs, but Induces Gut-Homing pDCs from Bone Marrow. AIDS Res Hum Retroviruses. 2014 Oct; 30 Suppl 1:A126-7. PMID: 25357350.
    View in: PubMed
  16. Li Q, Zeng M, Duan L, Voss JE, Smith AJ, Pambuccian S, Shang L, Wietgrefe S, Southern PJ, Reilly CS, Skinner PJ, Zupancic ML, Carlis JV, Piatak M, Waterman D, Reeves RK, Masek-Hammerman K, Derdeyn CA, Alpert MD, Evans DT, Kohler H, Müller S, Robinson J, Lifson JD, Burton DR, Johnson RP, Haase AT. Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry. J Immunol. 2014 Sep 15; 193(6):3113-25. PMID: 25135832; PMCID: PMC4157131.
  17. Shang L, Smith AJ, Duan L, Perkey KE, Qu L, Wietgrefe S, Zupancic M, Southern PJ, Masek-Hammerman K, Reeves RK, Johnson RP, Haase AT. NK cell responses to simian immunodeficiency virus vaginal exposure in naive and vaccinated rhesus macaques. J Immunol. 2014 Jul 01; 193(1):277-84. PMID: 24899503; PMCID: PMC4083479.
  18. Sasikala-Appukuttan AK, Kim HO, Kinzel NJ, Hong JJ, Smith AJ, Wagstaff R, Reilly C, Piatak M, Lifson JD, Reeves RK, Johnson RP, Haase AT, Skinner PJ. Location and dynamics of the immunodominant CD8 T cell response to SIV?nef immunization and SIVmac251 vaginal challenge. PLoS One. 2013; 8(12):e81623. PMID: 24349100; PMCID: PMC3857218.
  19. Carville A, Evans TI, Reeves RK. Characterization of circulating natural killer cells in neotropical primates. PLoS One. 2013; 8(11):e78793. PMID: 24244365; PMCID: PMC3823947.
  20. Song H, Josleyn N, Janosko K, Skinner J, Reeves RK, Cohen M, Jett C, Johnson R, Blaney JE, Bollinger L, Jennings G, Jahrling PB. Monkeypox virus infection of rhesus macaques induces massive expansion of natural killer cells but suppresses natural killer cell functions. PLoS One. 2013; 8(10):e77804. PMID: 24147080; PMCID: PMC3798392.
  21. Li H, Gillis J, Johnson RP, Reeves RK. Multi-functional plasmacytoid dendritic cells redistribute to gut tissues during simian immunodeficiency virus infection. Immunology. 2013 Oct; 140(2):244-9. PMID: 23746074; PMCID: PMC3784170.
  22. Evans TI, Reeves RK. All-trans-retinoic acid imprints expression of the gut-homing marker a4ß7 while suppressing lymph node homing of dendritic cells. Clin Vaccine Immunol. 2013 Oct; 20(10):1642-6. PMID: 23966557; PMCID: PMC3807207.
  23. Li H, Evans TI, Reeves RK. Loss of bone marrow NK cells during SIV infection is associated with increased turnover rates and cytotoxicity but not changes in trafficking. J Med Primatol. 2013 Oct; 42(5):230-6. PMID: 23898936; PMCID: PMC3777546.
  24. Hong HS, Rajakumar PA, Billingsley JM, Reeves RK, Johnson RP. No monkey business: why studying NK cells in non-human primates pays off. Front Immunol. 2013; 4:32. PMID: 23423644; PMCID: PMC3575030.
  25. Li H, Reeves RK. Functional perturbation of classical natural killer and innate lymphoid cells in the oral mucosa during SIV infection. Front Immunol. 2012; 3:417. PMID: 23316201; PMCID: PMC3539714.
  26. Alpert MD, Harvey JD, Lauer WA, Reeves RK, Piatak M, Carville A, Mansfield KG, Lifson JD, Li W, Desrosiers RC, Johnson RP, Evans DT. ADCC develops over time during persistent infection with live-attenuated SIV and is associated with complete protection against SIV(mac)251 challenge. PLoS Pathog. 2012; 8(8):e1002890. PMID: 22927823; PMCID: PMC3426556.
  27. Reeves RK, Evans TI, Gillis J, Wong FE, Kang G, Li Q, Johnson RP. SIV infection induces accumulation of plasmacytoid dendritic cells in the gut mucosa. J Infect Dis. 2012 Nov; 206(9):1462-8. PMID: 22711907; PMCID: PMC3529602.
  28. Reeves RK, Rajakumar PA, Evans TI, Connole M, Gillis J, Wong FE, Kuzmichev YV, Carville A, Johnson RP. Gut inflammation and indoleamine deoxygenase inhibit IL-17 production and promote cytotoxic potential in NKp44+ mucosal NK cells during SIV infection. Blood. 2011 Sep 22; 118(12):3321-30. PMID: 21791421; PMCID: PMC3179400.
  29. Fofana IB, Colantonio AD, Reeves RK, Connole MA, Gillis JM, Hall LR, Sato S, Audin CR, Evans DT, Shida H, Johnson RP, Johnson WE. Flow cytometry based identification of simian immunodeficiency virus Env-specific B lymphocytes. J Immunol Methods. 2011 Jul 29; 370(1-2):75-85. PMID: 21689659; PMCID: PMC3134132.
  30. Moreland AJ, Guethlein LA, Reeves RK, Broman KW, Johnson RP, Parham P, O'Connor DH, Bimber BN. Characterization of killer immunoglobulin-like receptor genetics and comprehensive genotyping by pyrosequencing in rhesus macaques. BMC Genomics. 2011 Jun 07; 12:295. PMID: 21645414; PMCID: PMC3125267.
  31. Colantonio AD, Bimber BN, Neidermyer WJ, Reeves RK, Alter G, Altfeld M, Johnson RP, Carrington M, O'Connor DH, Evans DT. KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif. PLoS Pathog. 2011 Mar; 7(3):e1001316. PMID: 21423672; PMCID: PMC3053351.
  32. Reeves RK, Evans TI, Fultz PN, Johnson RP. Potential confusion of contaminating CD16+ myeloid DCs with anergic CD16+ NK cells in chimpanzees. Eur J Immunol. 2011 Apr; 41(4):1070-4. PMID: 21360701; PMCID: PMC3106337.
  33. Reeves RK, Evans TI, Gillis J, Wong FE, Connole M, Carville A, Johnson RP. Quantification of mucosal mononuclear cells in tissues with a fluorescent bead-based polychromatic flow cytometry assay. J Immunol Methods. 2011 Mar 31; 367(1-2):95-8. PMID: 21315723; PMCID: PMC3071447.
  34. Reeves RK, Wei Q, Fultz PN. Mobilization of CD34+ progenitor cells in association with decreased proliferation in the bone marrow of macaques after administration of the Fms-like tyrosine kinase 3 ligand. Clin Vaccine Immunol. 2010 Aug; 17(8):1269-73. PMID: 20554805; PMCID: PMC2916240.
  35. Reeves RK, Evans TI, Gillis J, Johnson RP. Simian immunodeficiency virus infection induces expansion of alpha4beta7+ and cytotoxic CD56+ NK cells. J Virol. 2010 Sep; 84(17):8959-63. PMID: 20554780; PMCID: PMC2919045.
  36. Reeves RK, Gillis J, Wong FE, Yu Y, Connole M, Johnson RP. CD16- natural killer cells: enrichment in mucosal and secondary lymphoid tissues and altered function during chronic SIV infection. Blood. 2010 Jun 03; 115(22):4439-46. PMID: 20339088; PMCID: PMC2881505.
  37. Reeves RK, Wei Q, Stallworth J, Fultz PN. Systemic dendritic cell mobilization associated with administration of FLT3 ligand to SIV- and SHIV-infected macaques. AIDS Res Hum Retroviruses. 2009 Dec; 25(12):1313-28. PMID: 20001520; PMCID: PMC2828165.
  38. Salisch NC, Kaufmann DE, Awad AS, Reeves RK, Tighe DP, Li Y, Piatak M, Lifson JD, Evans DT, Pereyra F, Freeman GJ, Johnson RP. Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1. J Immunol. 2010 Jan 01; 184(1):476-87. PMID: 19949078; PMCID: PMC2810496.
  39. Reeves RK, Gillis J, Wong FE, Johnson RP. Vaccination with SIVmac239Deltanef activates CD4+ T cells in the absence of CD4 T-cell loss. J Med Primatol. 2009 Oct; 38 Suppl 1:8-16. PMID: 19863673; PMCID: PMC2810497.
  40. Reeves RK, Fultz PN. Characterization of plasmacytoid dendritic cells in bone marrow of pig-tailed macaques. Clin Vaccine Immunol. 2008 Jan; 15(1):35-41. PMID: 17989338; PMCID: PMC2223857.
  41. Reeves RK, Fultz PN. Disparate effects of acute and chronic infection with SIVmac239 or SHIV-89.6P on macaque plasmacytoid dendritic cells. Virology. 2007 Sep 01; 365(2):356-68. PMID: 17490699; PMCID: PMC2043480.
  42. Weaver CC, Burgess SC, Nelson PD, Wilkinson M, Ryan PL, Nail CA, Kelly-Quagliana KA, May ML, Reeves RK, Boyle CR, Coats KS. Placental immunopathology and pregnancy failure in the FIV-infected cat. Placenta. 2005 Feb-Mar; 26(2-3):138-47. PMID: 15708115.
    View in: PubMed
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