Derin Keskin
Adjunct Associate Professor, Computer Science
Dr. Derin Keskin has more than twenty years of teaching experience, and has taught courses related to human physiology, anatomy, and health informatics at BU’s Metropolitan College since 2015. Dr. Keskin is currently the lead immunologist with the Translational Immunogenomics Lab at Harvard Medical School, teaching affiliate Dana-Farber Cancer Center. Keskin also serves as an affiliated associate professor at Denmark Technical Institute. He additionally holds a position as an affiliated research scientist at the Broad Institute of MIT and Harvard. Keskin’s research focuses on vaccine immunotherapies, autoimmune diseases, and cancer immunology. He has been involved with preclinical development, such as efficacy and safety studies, in vaccine research and has more than a decade of experience in T cell-based vaccine design against cancers and viruses such as influenza, HIV, and HPV. Keskin has extensive experience planning and managing entire immunological projects, including people, study design, financials, execution, analysis, troubleshooting, and FDA/IND applications/reporting. He has been an ad hoc reviewer for journals such as Nature Cancer, Annals of Oncology, Molecular Medicine, Journal of Immunological Methods, Advances in Clinical Chemistry, Neurotoxicity Research, Journal of Investigative Dermatology, and the European Academy of Dermatology and Venereology Journal.
Courses
- MET CS 570 – Biomedical Sciences and Health IT
Scholarly Works
Select Publications
View all publications by Dr. Keskin.
Giacomo Oliveira, Kari Stromhaug, Susan Klaeger, Tomasz Kula, Dennie Frederick Tompers, Phuong Le, Juliet Forman, Teddy Huang, Shuqiang Li, Wandi Zhang, … , Sune Justesen, Gavin MacBeath, Steven Carr, Edward F. Fritsch, Nir Hacohen, Moshe Sade-Feldman, Kenneth J. Livak, Genevieve M. Boland, Patrick A. Ott, Derin B. Keskin, and Catherine J. Wu. “Defining the phenotype, specificity and avidity of anti-tumor CD8+ T cells in melanoma.” Nature 605, no. 7910 (2021): 532–538. doi: 10.1038/s41586-022-04682-5
Zhuting Hu, Donna E. Leet, Rosa L.Allesoe, Shuqiang Li, Giacomo Oliveira, Adrienne M. Luoma, Jinyan Liu, … , Dan H. Barouch, Kai Wucherpfennig, Edward F. Fritsch, Derin B. Keskin, Catherine J. Wu, and Patrick A. Ott. “Personal Neoantigen Vaccines Induce Persistent Memory T Cell Responses and Epitope Spreading in Melanoma Patients.” Nature Medicine 27, no. 3 (2021): 515–525. doi: 10.1038/s41591-020-01206-4
Sarkizova, S., Klaeger, S., Phuong, M. L., Letitia, W. L., Oliveira, G., … , Zhang, GL., Clauser, K. L., Hacohen, N., Carr, S. A., Wu, C. J., and Keskin, D. B. “Improved prediction of endogenously presented HLA class I epitopes in human tumors based on 95 mono-allelic peptidomes.” Nature Biotechnology 38, no. 2 (2020):199–209. doi: 10.1038/s41587-019-0322-9
Keskin, D. B., Anandappa, A. J., Sun, J., Tirosh, I., … , Wu, C. J., and Reardon, D. A. “Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial.” Nature 565, no. 7738 (2019): 234–239. doi: 10.1038/s41586-018-0792-9
Shukla, S. S., Bachireddy, P., Schilling, B., Galonska, C., Zhan, Q., Lee, P.C., Keskin, D. B. et al. “Cancer-germline antigens discriminate clinical outcome to CTLA4 blockade.” Cell 173, no. 3 (2018): 624–633. DOI: 10.1016/j.cell.2018.03.026
Bae, J., Hideshima, T., Zhang, GL., Zhou, J., Keskin, D. B., Munshi, N. C., and Anderson, K. C. “Identification and characterization of HLA-A24 specific XBP1, CD138 (Syndecan-1), and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma.” Leukemia 32, no. 3 (2017): 752–764. DOI: 10.1038/leu.2017.316
Yoshikawa, A., Bi, K., Keskin, D. B., Zhang, G., Reinhold, B., and Reinherz, E. L. “TCR-pMHC encounter differentially regulates transcriptomes of- tissue-resident CD8 T cells.” European Journal of Immunology 28, no. 1 (2017): 128–150. DOI: 10.1002/eji.201747174
Ott, P. A., Hu, Z., Keskin, D. B. et al. “An Immunogenic Personal Neoantigen Vaccine for Patients with Melanoma.” Nature 547, no. 7662 (2017): 217–221. DOI: 10.1038/nature22991
*Abelin, J. G., *Keskin, D. B., *Sarkizova, S., Hartigan, C.R., Zhang, W., Sidney, J., Stevens, J., Lane, W., Zhang, GL., Eisenhaure, T. M., Clauser, K. R., Hacohen, N., Rooney, M. S., Carr, S. A., and Wu, C. J. “Mass Spectrometry Profiling of HLA-Associated Peptidomes in Mono-allelic Cells Enables More Accurate Epitope Prediction.” Immunity 46, no. 2 (2017): 315–326. DOI: 10.1016/j.immuni.2017.02.007
Tabansky, I., Messina, M. D., Bangeranye, C., Goldstein, J., Blitz-Shabbir, K. M., Machado, S., Jeganathan, V., Wright, P., Najjar, S., Cao, Y., Sands, W., Keskin, D. B., and Stern, J. N. “Advancing drug delivery systems for the treatment of multiple sclerosis.” Immunologic Research 63, no. 1–3 (2015) 58–69. DOI: 10.1007/s12026-015-8719-0
Keskin, D. B., Reinhold, B., Zhang, GL., Ivanov, A., Karger, B., and Reinherz, E. L. “Reply to van de Sandt and Rimmelzwann: Matching epitope display with functional avidity.” In Proceedings of the National Academy of Sciences of the United States of America 112, no. 19 (2015): E2418. DOI: 10.1073/pnas.1503931112
Bae, J., Keskin, D. B., Cowens, K., Lee, AH., Dranoff, G., Munshi, N. C., and Anderson, K. C. “Lenalidomide polarizes Th1-specific Anti-tumor immune response and expands XBP1 antigen specific central memory CD3+CD8+ T cells against various tumors.” Journal of Leukemia 3, no. 2 (2015): 178. DOI: 10.4172/2329-6917.1000178
Keskin, D. B., Reinhold, B., Zhang, GL., Ivanov, A., Karger, B., and Reinherz, E. L. “Physical detection of influenza A epitopes identifies a silent subset on human lung epithelium evading natural CD8 T cell immunity.” In Proceedings of the National Academy of Sciences of the United States of America 112, no. 7 (2015): 2151–6. DOI: 10.1073/pnas.1423482112
Das, D. K., Feng, Y., Mallis, R. J., Li, X., Keskin, D. B., Hussey, R. E., Brady, S. K., Wang, JH., Wagner, G., Reinherz, E. L., and Lang, M. J. “A force-dependent transition in the T cell receptor subunit allosterically regulates peptide discrimination and pMHC bond lifetime.” In Proceedings of the National Academy of Sciences of the United States of America 112, no. 5 (2015): 1517–22. DOI: 10.1073/pnas.1424829112
Reinherz, E. L., Keskin, D. B., Reinhold, B. “Forward Vaccinology: CTL Targeting Based upon Physical Detection of HLA-Bound Peptides.” Frontiers in Immunology vol. 5 (2014): 418. DOI: 10.3389/fimmu.2014.00418
Bae, J., Samur, M., Munshi, A., Hideshima, T., Kimmelman, A., Lee, AH., Keskin, D. B., Dranoff, G., Anderson, K. C., Munshi, N. C. “Heteroclitic XBP1 Peptides Evoke Tumor-Specific Memory Cytotoxic T Lymphocytes against Breast Cancer, Colon Cancer, and Pancreatic Cancer Cells.” Oncoimmunology 3, no. 12 (2014): e970914. DOI: 10.4161/21624011.2014.970914
Zhang, GL., Keskin, D. B., Lin, HN., Lin, H. H., DeLuca, D. S., Leppanen, S., Milford, E. L., Reinherz, E. L., Brusic, V. “Human Leukocyte Antigen typing using a knowledge base coupled with a high throughput oligonucleotide probe array analysis.” Frontiers in Immunology vol. 5 (2014): 597. DOI: 10.3389/fimmu.2014.00597
Brazin, K. N., Mallis, R. J., Li, C., Keskin, D. B., Arthanari, H., Gao, Y., Wu, SL., Karger, B. L., Wagner, G., and Reinherz, E. L. “Constitutively oxidized CxxC motifs within each CD3 heterodimeric ectodomains of the T cell receptor complex enforce the conformation of juxtaposed segments.” Journal of Biological Chemistry 289, no. 27 (2014): 18880-92. DOI: 10.1074/jbc.M114.574996
Rajasagi, M., Shukla, S., Keskin, D. B., Kim, J., Zhang, W., DeLuca, D., Sidney, J., Brusic, V., Neuberg, D. S., Getz, G., Lander, E. S., Hacohen, N., and Wu, C. J. “Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia.” Blood 124, no. 3 (2014): 453–62. DOI: 10.1182/blood-2014-04-567933
Tabansky, I., Lenarcic, A., Draft, R., Loulier, K., Keskin, D. B., Rosains, J., Rivera-Feliciano, J., Lichtman, J., Livet, J., Stern, J. N., Sanes, J. R., and Eggan K. “Developmental bias in cleavage-stage mouse blastomeres.” Current Biology 23, no. 1 (2013): 21–31. DOI: 10.1016/j.cub.2012.10.054
Cai, A., Keskin, D. B., DeLuca, D., Alonso, A., Zhang, W., Zhang, GL., Hammond, N. N., Nardi, V., Stone, R., Neuberg, D., Sidney, J., Brusic, V., and Wu, C. J. “Mutated BCR-ABL Generates Immunogenic T Cell Epitopes In CML Patients.” Clinical Cancer Research 18, no. 20 (2012): 5761–72. DOI: 10.1158/1078-0432.CCR-12-1182
Keskin, D. B., Reinhold, B., Lee SY, Zhang, GL., Lank S, O’Connor D, Berkowitz RS, Brusic, V., Kim SJ, Reinherz, E. L. “Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens. Frontiers in Immunology vol. 2 (2011): 75. DOI: 10.3389/fimmu.2011.00075
Lank, S. M., Golbach, B. A., Creager, H. M., Wiseman, R. W., Keskin, D. B., Reinherz, E. L., Brusic, V., and O’Connor, D. H. “Ultra-high resolution HLA genotyping and allele discovery by highly multiplexed cDNA amplicon pyrosequencing.” BMC Genomics vol. 13 (2012): 378. DOI: 10.1186/1471-2164-13-378
Riemer, A. B., Keskin, D. B., and Reinherz, E. L. “Identification of valid reference genes for gene expression studies in primary and malignant human keratinocytes in different immunological experimental conditions.” Experimental Dermatology 21, no. 8 (2012): 625–9.
Zakka, L. R., Fradkov, E., Keskin, D. B., Tabansky, I., Stern, J. N., and Ahmed, A. R. “The role of natural killer cells in autoimmune blistering diseases.” Autoimmunity 45, no. 1 (2012): 44–54. DOI: 10.3109/08916934.2011.606446
Olsen, L. R., Zhang, GL., Keskin, D. B., Reinherz, E. L., Brunak, S., and Brusic, V. “Conservation analysis of dengue virus T-cell epitope-based vaccine candidates using peptide block entropy analysis.” Frontiers in Immunology vol. 2 (2011): 69. DOI: 10.3389/fimmu.2011.00069
DeLuca, D. S., Keskin, D. B., Zhang, GL., Reinherz, E. L., and Brusic, V. “PB1-F2 Finder: scanning influenza sequences for PB1-F2 encoding RNA segments.” BMC Bioinformatics 12 Suppl 13 (2011): S6. DOI: 10.1186/1471-2105-12-S13-S6
Touma, M., Keskin, D. B., Clayton, L. K., and Reinherz, E. L. “Impaired B cell development and function in the absence of IkappaBNS.” Journal of Immunology 187, no. 8 (2011): 3942–52. DOI: 10.4049/jimmunol.1002109
Zhang, GL., Lin, H. H., Keskin, D. B., Reinherz, E. L., and Brusic, V. “Dana-Farber repository for machine learning in immunology.” Journal of Immunological Methods 374, no. 1–2 (2011): 1825. DOI: 10.1016/j.jim.2011.07.007
Zhang, Z., Tongchusak, S., Mizukami, Y., Kang, Y. J., Ioji, T., Touma, M., Reinhold, B., Keskin, D. B., Reinherz, E. L., and Sasada, T. “Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery.” Biomaterials 32, no. 14 (2011): 3666–78. DOI: 10.1016/j.biomaterials.2011.01.067
Zhang, GL., DeLuca, D.; Keskin, D. B., Reinherz, E. L.; Chitkushev, L., Zlateva, T., and Brusic, V. “MULTIPRED2: A computational system for large-scale identification of peptides predicted to bind to HLA supertypes and alleles.” Journal of Immunological Methods 374, no. 1–2 (2011): 5361. DOI: 10.1016/j.jim.2010.11.009
Zakka, L. R., Keskin, D. B., Reche, P., and Ahmed, A. R. “Relationship between target antigens and major histocompatibility complex (MHC) class II genes in producing two pathogenic antibodies simultaneously.” Clinical and Experimental Immunology 162, no. 2 (2010): 224–36. DOI: 10.1111/j.1365-2249.2010.04239.x
Reinhold, B., Keskin, D. B., and Reinherz, E. L. “Molecular detection of targeted major histocompatibility complex I-bound peptides using a probabilistic measure and nanospray MS3 on a hybrid quadrupole-linear ion trap.” Analytical Chemistry 82, no. 21 (2010): 9090–9.
Mabrouk, D., Gürcan, H. M., Keskin, D. B., Christen, W. G., and Ahmed, A. R. “Association between cancer and immunosuppressive therapy—analysis of selected studies in pemphigus and pemphigoid.” Annals of Pharmacotherapy 44, no. 11 (2010): 1770–6. DOI: 10.1345/aph.1P309
*Stern, J. N., *Keskin, D. B., Kato, Z., Waldner, H., Schallenberg, S., Anderson, A., von Boehmer, H., Kretschmer, K., and Strominger, J. L. “Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells.” In Proceedings of the National Academy of Sciences of the United States of America 107, no. 40 (2010): 17280–5. DOI: 10.1073/pnas.1010263107
*Riemer, A. B., *Keskin, D. B., Zhang, G., Handley, M., Anderson, K. S., Brusic, V., Reinhold, B., and Reinherz, E. L. “A conserved E7-derived cytotoxic T lymphocyte epitope expressed on human papillomavirus 16-transformed HLA-A2+ epithelial cancers.” Journal of Biological Chemistry 285, no. 38 (2010): 29608–22. DOI: 10.1074/jbc.M110.126722
*Gürcan, H. M., *Keskin, D. B., and Ahmed, A. R. “Information for healthcare providers on general features of IGIV with emphasis on differences between commercially available products.” Autoimmunity Reviews 9, no. 8 (2010): 553–9. DOI: 10.1016/j.autrev.2010.03.003
Ofran, Y., Kim, H. T., Brusic, V., Blake, L., Mandrell, M., Wu, C. J., Sarantopoulos, S., Bellucci, R., Keskin, D. B., Soiffer, R. J., Antin, J. H., and Ritz, J. “Diverse patterns of T-cell response against multiple newly identified human Y chromosome-encoded minor histocompatibility epitopes.” Clinical Cancer Research 16, no. 5 (2010): 1642–51. DOI: 10.1158/1078-0432.CCR-09-2701
Bhasin, M., Yuan, L., Keskin, D. B., Libermann, T. A., and Oettgen, P. “Bioinformatics identification and characterization of human endothelial cell-restricted genes.” BMC Genomics vol. 11 (2010): 342. DOI: 10.1186/1471-2164-11-342
*Stern, J. N., *Keskin, D. B., Romero, V., Zuniga, J., Encinales, L., Li, C., Awad, C., Yunis, E. J. “Molecular signatures distinguishing active from latent tuberculosis in peripheral blood mononuclear cells, after in vitro antigenic stimulation with purified protein derivative of tuberculin (PPD) or Candida: a preliminary report.” Immunologic Research 45, no. 1 (2009): 1–12. DOI: 10.1007/s12026-008-8024-2
*Gürcan, H. M., *Keskin, D. B., Stern, J. N., Nitzberg, M. A., Shekhani, H., and Ahmed, A. R. “A review of the current use of rituximab in autoimmune diseases.” International Immunopharmacology 9, no. 1 (2009): 10–25. DOI: 10.1016/j.intimp.2008.10.004
Chung, J., Serezani, C. H., Huang, S. K., Stern, J. N., Keskin, D. B., Jagirdar, R., Brock, T. G., Aronoff, D. M., Peters-Golden, M. “Rap1 activation is required for Fc gamma receptor-dependent phagocytosis.” Journal of immunology 181, no. 8 (2008): 5501–9. DOI: 10.4049/jimmunol.181.8.5501
Stern, J. N., and Keskin, D. B. “Strategies for the identification of loci responsible for the pathogenesis of multiple sclerosis.” Cellular & Molecular Biology Letters 13, no. 4 (2008): 656–66. DOI: 10.2478/s11658-008-0030-9
*Stern, J. N., *Keskin, D. B., Zhang, H., Lv, H., and Strominger, J. L. “Amino acid copolymer-specific IL-10-secreting regulatory T cells that ameliorate autoimmune diseases in mice.” In Proceedings of the National Academy of Sciences of the United States of America 105, no. 13 (2008): 5172–6. DOI: 10.1073/pnas.0712131105
*Stern, J. N., *Keskin, D. B., Barteneva, N., Zuniga, J., Yunis, E. J., and Ahmed, A. R. “Possible role of natural killer cells in pemphigus vulgaris—preliminary observations.” Clinical and Experimental Immunology 152, no. 3 (2008): 472–81. DOI: 10.1111/j.1365-2249.2008.03638.x
Keskin, D. B., Stern, J. N., Fridkis-Hareli, M., and Ahmed, A. R. “Cytokine profiles in pemphigus vulgaris patients treated with intravenous immunoglobulins as compared to conventional immunosuppressive therapy.” Cytokine 41, no. 3 (2008): 315–21. DOI: 10.1016/j.cyto.2007.12.007
Touma, M., Antonini, V., Kumar, M., Osborn, S. L., Bobenchik, A. M., Keskin, D. B., Connolly, J. E., Grusby, M. J., Reinherz, E. L., and Clayton, L. K. “Functional role for I kappa BNS in T cell cytokine regulation as revealed by targeted gene disruption.” Journal of Immunology 179, no. 3 (2007): 1681–92. DOI: 10.4049/jimmunol.179.3.1681
Keskin, D. B., Allan, D. S., Rybalov, B., Andzelm, M. M., Stern, J. N., Kopcow, H. D., Koopman, L. A., and Strominger, J. L. “TGFbeta promotes conversion of CD16+ peripheral blood NK cells into CD16- NK cells with similarities to decidual NK cells.” In Proceedings of the National Academy of Sciences of the United States of America 104, no. 9 (2007): 3378–83. DOI: 10.1073/pnas.0611098104
Keskin, D. B., Marshall, B., Munn, D., Mellor, A. L., and Gearhart, D. A. “Decreased protein nitration in macrophages that overexpress indoleamine 2, 3-dioxygenase.” Cellular & Molecular Biology Letters 12, no. 1 (2007): 82–102. DOI: 10.2478/s11658-006-0048-9
*Reche, P. A., *Keskin, D. B., Hussey, R. E., Ancuta, P., Gabuzda, D., and Reinherz, E. L. “Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes.” Medical Immunology vol. 5 (2006): 1. DOI: 10.1186/1476-9433-5-1
Illés, Z., Stern, J. N. H., Keskin, D. B., Reddy, J., Kuchroo, V. K., and Strominger, J. L. “Copolymer effects on microglia and T cells in the central nervous system of humanized mice.” European Journal of Immunology 35, no. 12 (2005): 3683–93. DOI: 10.1002/eji.200526121
Stern, J. N., Illés, Z., Reddy, J., Keskin, D. B., Brosnan, C., Fridkis-Hareli, M., Kuchroo, V. K., and Strominger, J. L. “Peptide 15-mers of defined sequence that substitute for random amino acid copolymers in amelioration of experimental autoimmune encephalomyelitis.” In Proceedings of the National Academy of Sciences of the United States of America 102, no. 5 (2005): 1620–5. DOI: 10.1073/pnas.0409022102
Stern, J. N., Illés, Z., Reddy, J., Keskin, D. B., Sheu, E., Fridkis-Hareli, M., Nishimura, H., Santambrogio, L., Brosnan, C. F., Kuchroo, V. K., and Strominger, J. L. “Amelioration of PLP 139-151-induced EAE in SJL mice by modified amino acid copolymers and their mechanisms.” In Proceedings of the National Academy of Sciences of the United States of America vol. 101 (2004): 11743–8.
Mellor, A. L., Munn, D., Chandler, P., Keskin, D. B., Johnson, T., Marshall, B., Jhaver, K., Baban, B. “Tryptophan catabolism and T cell responses.” Advances in Experimental Medicine and Biology vol. 527 (2003): 27–35. DOI: 10.1007/978-1-4615-0135-0_3
Keskin, D. B. “Regulation of T cell immunity by cells expressing Indoleamine 2.3-dioxygenase.” PhD thesis, Medical College of Georgia (ProQuest publishers, 2003). ISBN: 97804937428310
Munn, D. H., Sharma, M. D., Lee, J. R., Jhaver, K. G., Johnson, T. S., Keskin, D. B., Marshall, B., Antonia, S. J., Burgess, R., Slingluff, C. L., and Mellor, A. L. “Potential regulatory function of human dendritic cells expressing indoleamine 2,3, dioxygenase.” Science 297, no. 5588 (2002): 1867–70. DOI: 10.1126/science.1073514
Mellor, A. L., Keskin, D. B., Johnson, T., Chandler, P., and Munn, D. “Cells expressing IDO inhibit T cell responses.” Journal of Immunology 168, no. 8 (2002):3771–3776. DOI: https://doi.org/10.4049/jimmunol.168.8.3771
Mellor, A. L., Chandler, P., Lee, G. K., Johnson, T., Keskin, D. B., Lee, J., and Munn, D. H. “Indoleamine 2,3 dioxygenase, immunosuppression and pregnancy.” Journal of Reproductive Immunology 57, no. 1–2 (2002): 143–50. DOI: 10.1016/s0165-0378(02)00040-2
Fallarino, F., Vacca, C., Orabona, C., Belladonna, M., Bianchi, R., Marshall, B., Keskin, D. B., Mellor, A. L., Fioretti, M. C., Grohmann, U., and Puccetti, P. “Functional expression of indoleamine 2,3-dioxygenase by murine CD8 alpha(+) dendritic cells.” International Immunology 14, no. 1 (2002): 65–8. DOI: 10.1093/intimm/14.1.65
Marshall, B., Keskin, D. B., and Mellor, A. L. “Regulation of prostaglandin synthesis and cell adhesion by a Tryptophan catabolizing enzyme.” BMC Biochemistry vol. 2 (2001): 5. DOI: 10.1186/1471-2091-2-5
*Contributed equally as first author.
Research Grants
2022: Principal Investigator (PI), R01 HL157174-01A1: “Systematic identification of minor histocompatibility antigens to address GVHD.”
2018: Principal Investigator (PI), R21 CA216772-01A1: “Physical detection of HLA-C binding peptides to identify and predict immunogenic personal neoepitopes for improving cancer vaccines.”
2017: Principal Investigator (PI), DFCI/Medical Oncology Departmental Grant.
2016–2017: Principal Investigator (PI), 2P50CA10194211A1: DF/HCC Kidney Cancer SPORE
Patents
Keskin, D. B. “MS-based accurate epitope prediction algorithms.” Broad Institute. Filed in 2017.
Reinherz, E. L., Brusic, V., Zhang, GL., Keskin, D. B., and DeLuca, D. S. “Oligonucleotide array for precise HLA typing.” 00530-00287P01, December 2010.