Dr. Rasmi Thomas obtained her Ph.D. in Biotechnology from the Rajiv Gandhi Center for Biotechnology at the University of Kerala, India. She completed her postdoctoral training with Dr. Mary Carrington from the National Cancer Institute, NIH in Frederick, MD.
The Laboratory of Integrative Multiomics utilizes cutting-edge next-generation sequencing (NGS) technologies to identify variation in genes involved in host-pathogen interaction. We support studies related to disease acquisition, pathogenesis, response to vaccination or treatment outcomes.
In order to advance MHRP’s mission to develop an effective vaccine and eradicate HIV, we employ laboratory and bioinformatic methods to characterize host genetic, transcriptomic, epigenetic and microbiome variation using unbiased genome-wide sequencing approaches. Previous studies using gene chips have been limited, as they only screen a targeted number of variations and are inherently biased towards particular populations. Our lab uses unbiased NGS technologies to study diverse populations across Asia, Africa, Europe and the Americas, screening genetic variations and identifying their functional basis. NGS methods for genotyping immune response genes that have previously been implicated in HIV-1 disease pathogenesis, such as the Human Leukocyte Antigen (HLA), have been developed in the laboratory and support ongoing clinical and research activities. RNA-Sequencing (RNA-Seq) technology is being used for whole transcriptome expression profiling to elucidate mRNA gene expression and to analyze non-coding RNA.
Relevant to MHRP’s mission to develop an effective prophylactic vaccine, we recently showed that a vaccine-induced gene signature correlates with protection in both non-human primate and human trials. We are at the forefront of developing these RNA-Seq technologies for analysis of transcriptomes of single cells and detection of transcripts from intracellular pathogens. Integrating proteomics with other ‘omics’ datasets to shed light on mechanisms is another important focus of the group. Microbiome sequencing of gut and genital tract mucosa of HIV-1 infected patients by NGS is also being performed to support activities in other sections at MHRP. By using a range of innovative multifaceted strategies this group continues to make discoveries that can be applied to the central mission of MHRP to fight HIV.
Ehrenberg PK, Shangguan S, Issac B, Alter G, Geretz A, Izumi T, Bryant C, Eller MA, Wegmann F, Apps R, Creegan M, Bolton DL, Sekaly RP, Robb ML, Gramzinski RA, Pau MG, Schuitemaker H, Barouch DH, Michael NL, Thomas R. A vaccine-induced gene expression signature correlates with protection against SIV and HIV in multiple trials. Sci Transl Med. 2019 Aug 28;11(507). doi: 10.1126/scitranslmed.aaw4236.
Yarzabek B, Zaitouna AJ, Olson E, Silva GN, Geng J, Geretz A, Thomas R, Krishnakumar S, Ramon DS, Raghavan M. Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity. Elife. 2018 Jul 10;7. pii: e34961.
Martin MP, Naranbhai V, Shea PR, Qi Y, Ramsuran V, Vince N, Gao X, Thomas R, Brumme ZL, Carlson JM, Wolinsky SM, Goedert JJ, Walker BD, Segal FP, Deeks SG, Haas DW, Migueles SA, Connors M, Michael N, Fellay J, Gostick E, Llewellyn-Lacey S, Price DA, Lafont BA, Pymm P, Saunders PM, Widjaja J, Wong SC, Vivian JP, Rossjohn J, Brooks AG, Carrington M. Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. J Clin Invest. 2018 May 1;128(5):1903-1912.
Prentice HA, Tomaras GA, Geraghty DE, Apps R, Fong Y, Ehrenberg PK, Rolland M, Kijak GH, Krebs SJ, Nelson W, DeCamp A, Shen X, Yates NL, Zolla-Pazner S, Nitayaphan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Ferrari G, McElrath MJ,Montefiori DC, Bailer RT, Koup RA, O’Connell RJ, Robb ML, Michael NL, Gilbert PB, Kim JK, Thomas R. HLA class II genes modulate vaccine-induced antibody responses to impact HIV-1 acquisition. 2015. ScienceTranslational Medicine 15:296ra112.
Baldwin KM, Ehrenberg PK, Geretz A, Prentice A, Nitayaphan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, O’Connell RJ, Kim JK, Thomas R. HLA class II diversity in the placebo arm of the RV144 Thai Phase 3 HIV vaccine clinical trial. Tissue Antigens 85:117-126.
Ehrenberg PK, Baldwin KM, Geretz A, Apps, R, Polonis, V, Robb ML, Kim JK, Nelson, M, Thomas R. 2014. High-throughput multiplex HLA genotyping by next-generation sequencing using multi-locus individual tagging. BMC Genomics 15:864.
Prentice A, Ehrenberg PK, Baldwin KM, Geretz A, Andrews C, Nitayaphan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, O’Connell RJ, Robb ML, Kim JK, Nelson, M, Thomas R. 2014. HLA class I, KIR and genome-wide SNP diversity in the RV144 Thai Phase 3 HIV vaccine clinical trial. Immunogenetics 66:299-310.
Apps R, Qi Y, Carlson JM, Chen H, Gao X, Thomas R, Yuki Y, Del Prete GQ, Goulder P, Brumme ZL, Brumme CJ, John M, Mallal S, Nelson G, Bosch R, Heckerman D, Stein JL, Soderberg KA, Moody MA, Denny TN, Zeng X, Fang J, Moffett A, Lifson JD, Goedert JJ, Buchbinder S, Kirk GD, Fellay J, McLaren P, Deeks SG, Pereyra F, Walker B, Michael NL, Weintrob A, Wolinsky S, Liao W, Carrington M. Influence of HLA-C expression level on HIV control. Science. 2013 Apr 5;340(6128):87-91.
Thomas R, Thio CL, Apps R, Qi Y, Gao X, Marti D, Stein JL, Soderberg KA, Moody MA, Goedert JJ, Kirk GD, Hoots KW, Wolinsky S, and Carrington M. 2012. A novel variant marking HLA-DP expression levels predicts recovery from Hepatitis B Virus infection. Journal of Virology 12: 6979-85.
Thomas R, Apps R, Qi Y, O’Connor G, Ge D, Fellay J, Martin JN, Margolick J, Goedert JJ, Buchbinder S, Kirk GD, Telenti A, Deeks SG, Walker BD, Goldstein D, McVicar DW, Moffett A and Carrington M. 2009. HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C. Nature Genetics 12: 1290-1294.
Complete list of published work: