Major Areas of Research
- Single cell RNASeq and CITEseq analysis of innate and adaptive immune responses
- Dynamics of IG and TR repertoires in response to vaccination and infection
- Somatic hypermutation and antibody phylogenetics
- Impact of IG genetics on immune outcomes
Program Description
The Integrative Bioinformatics of Immune Systems (IBIS) Core is the central bioinformatic resource for all repertoire and “omics” studies in the VRC, offering coordinated staffing and planning for multi-section and external collaborations, such as the ongoing SARS-CoV-2 response efforts. Specific research areas in the IBIS Core include transcriptomic analysis of both innate and adaptive immune cells, T cell receptor repertoire analysis, B cell receptor sequence and phylogenetic analysis, and analysis of immune cell population dynamics. In addition, we work closely with the Genome Analysis, Humoral Immunology, Structural Bioinformatics Cores, and the Vaccine Immunology Program to prioritize experiments and analyses that will best advance the scientific objectives of the VRC.
Biography
Dr. Schramm earned his Ph.D. from the University of Pennsylvania in 2012 and completed a postdoctoral fellowship at Columbia University prior to joining the VRC as a staff scientist in 2016. Dr. Schramm has been a pioneer in the longitudinal phylogenetic analysis of B cell clonal lineages and developed the SONAR analysis suite to facilitate those studies. He also has significant research interests in IG V gene substitution profiles and immunogenetics. As chief of the IBIS Core, Dr. Schramm designs and leads large-scale scRNASeq analyses of innate and adaptive immune cells dynamics in infection and vaccination. Beyond the VRC, Dr. Schramm is a founding member of the AIRR Community organization and serves as co-chair of the Software Working Group.
Selected Publications
Corbett KS, Gagne M, Wagner DA, Connell SO, Narpala SR, Flebbe DR, Andrew SF, Davis RL, Flynn B, Johnston TS, Stringham C, Lai L, Valentin D, Van Ry A, Flinchbaugh Z, Werner AP, Moliva JI, Sriparna M, O'Dell S, Schmidt SD, Tucker C, Choi A, Koch M, Bock KW, Minai M, Nagata BM, Alvarado GS, Henry AR, Laboune F, Schramm CA, Zhang Y, Wang L, Choe M, Boyoglu-Barnum S, Shi W, Lamb E, Nurmukhambetova ST, Provost SJ, Donaldson MM, Marquez J, Todd JM, Cook A, Dodson A, Pekosz A, Boritz E, Ploquin A, Doria-Rose N, Pessaint L, Andersen H, Foulds KE, Misasi J, Wu K, Carfi A, Nason MC, Mascola J, Moore IN, Edwards DK, Lewis MG, Suthar MS, Roederer M, McDermott A, Douek DC, Sullivan NJ, Graham BS, Seder RA. Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates. bioRxiv [Preprint]. 2021 Aug:2021.08.11.456015.
Wang L, Zhou T, Zhang Y, Yang ES, Schramm CA, Shi W, Pegu A, Oloniniyi OK, Henry AR, Darko S, Narpala SR, Hatcher C, Martinez DR, Tsybovsky Y, Phung E, Abiona OM, Antia A, Cale EM, Chang LA, Choe M, Corbett KS, Davis RL, DiPiazza AT, Gordon IJ, Hait SH, Hermanus T, Kgagudi P, Laboune F, Leung K, Liu T, Mason RD, Nazzari AF, Novik L, O'Connell S, O'Dell S, Olia AS, Schmidt SD, Stephens T, Stringham CD, Talana CA, Teng IT, Wagner DA, Widge AT, Zhang B, Roederer M, Ledgerwood JE, Ruckwardt TJ, Gaudinski MR, Moore PL, Doria-Rose NA, Baric RS, Graham BS, McDermott AB, Douek DC, Kwong PD, Mascola JR, Sullivan NJ, Misasi J. Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Science. 2021 Aug;373(6556):eabh1766.
Mukhamedova M, Wrapp D, Shen CH, Gilman MSA, Ruckwardt TJ, Schramm CA, Ault L, Chang L, Derrien-Colemyn A, Lucas SAM, Ransier A, Darko S, Phung E, Wang L, Zhang Y, Rush SA, Madan B, Stewart-Jones GBE, Costner PJ, Holman LA, Hickman SP, Berkowitz NM, Doria-Rose NA, Morabito KM, DeKosky BJ, Gaudinski MR, Chen GL, Crank MC, Misasi J, Sullivan NJ, Douek DC, Kwong PD, Graham BS, McLellan JS, Mascola JR. Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses. Immunity. 2021 Apr;54(4):769-780.e6.
Roark RS, Li H, Williams WB, Chug H, Mason RD, Gorman J, Wang S, Lee FH, Rando J, Bonsignori M, Hwang KK, Saunders KO, Wiehe K, Moody MA, Hraber PT, Wagh K, Giorgi EE, Russell RM, Bibollet-Ruche F, Liu W, Connell J, Smith AG, DeVoto J, Murphy AI, Smith J, Ding W, Zhao C, Chohan N, Okumura M, Rosario C, Ding Y, Lindemuth E, Bauer AM, Bar KJ, Ambrozak D, Chao CW, Chuang GY, Geng H, Lin BC, Louder MK, Nguyen R, Zhang B, Lewis MG, Raymond DD, Doria-Rose NA, Schramm CA, Douek DC, Roederer M, Kepler TB, Kelsoe G, Mascola JR, Kwong PD, Korber BT, Harrison SC, Haynes BF, Hahn BH, Shaw GM. Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth. Science. 2021 Jan;371(6525):eabd2638.
Dr Schramm is a computational immunologist studying B cell biology through sequencing. A significant portion of his research is focused on antibody development and evolution with an emphasis on applications to vaccine design. Rare, broadly neutralizing antibodies against HIV-1 are of particular interest, as the induction of such bnAbs by vaccination is thought to be one of the best strategies for ending the global epidemic. Dr. Schramm also studies patterns of somatic hypermutation and the emergence of specific rare substitutions with great functional importance. Other areas of research include immunogenetics and understanding how variation in the germline repertoire impacts the immune response to infection or vaccination, as well as efforts to investigate immune responses through single cell transcriptomics.
Lima NS, Mukhamedova M, Johnston TS, Wagner DA, Henry AR, Wang L, Yang ES, Zhang Y, Birungi K, Black WP, O'Dell S, Schmidt SD, Moon D, Lorang CG, Zhao B, Chen M, Boswell KL, Roberts-Torres J, Davis RL, Peyton L, Narpala SR, O'Connell S, Wang J, Schrager A, Talana CA, Leung K, Shi W, Khashab R, Biber A, Zilberman T, Rhein J, Vetter S, Ahmed A, Novik L, Widge A, Gordon I, Guech M, Teng IT, Phung E, Ruckwardt TJ, Pegu A, Misasi J, Doria-Rose NA, Gaudinski M, Koup RA, Kwong PD, McDermott AB, Amit S, Schacker TW, Levy I, Mascola JR, Sullivan NJ, Schramm CA, Douek DC. Convergent epitope specificities, V gene usage and public clones elicited by primary exposure to SARS-CoV-2 variants. bioRxiv [Preprint]. 2022 Mar 29:2022.03.28.486152.
Wang L, Zhou T, Zhang Y, Yang ES, Schramm CA, Shi W, Pegu A, Oloniniyi OK, Henry AR, Darko S, Narpala SR, Hatcher C, Martinez DR, Tsybovsky Y, Phung E, Abiona OM, Antia A, Cale EM, Chang LA, Choe M, Corbett KS, Davis RL, DiPiazza AT, Gordon IJ, Hait SH, Hermanus T, Kgagudi P, Laboune F, Leung K, Liu T, Mason RD, Nazzari AF, Novik L, O'Connell S, O'Dell S, Olia AS, Schmidt SD, Stephens T, Stringham CD, Talana CA, Teng IT, Wagner DA, Widge AT, Zhang B, Roederer M, Ledgerwood JE, Ruckwardt TJ, Gaudinski MR, Moore PL, Doria-Rose NA, Baric RS, Graham BS, McDermott AB, Douek DC, Kwong PD, Mascola JR, Sullivan NJ, Misasi J. Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Science. 2021 Aug 13;373(6556):eabh1766.
Olson BJ, Moghimi P, Schramm CA, Obraztsova A, Ralph D, Vander Heiden JA, Shugay M, Shepherd AJ, Lees W, Matsen FA 4th. sumrep: A Summary Statistic Framework for Immune Receptor Repertoire Comparison and Model Validation. Front Immunol. 2019 Nov 1;10:2533.
Andrews SF, Chambers MJ, Schramm CA, Plyler J, Raab JE, Kanekiyo M, Gillespie RA, Ransier A, Darko S, Hu J, Chen X, Yassine HM, Boyington JC, Crank MC, Chen GL, Coates E, Mascola JR, Douek DC, Graham BS, Ledgerwood JE, McDermott AB. Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin. Immunity. 2019 Aug 20;51(2):398-410.e5.
Krebs SJ, Kwon YD, Schramm CA, Law WH, Donofrio G, Zhou KH, Gift S, Dussupt V, Georgiev IS, Schätzle S, McDaniel JR, Lai YT, Sastry M, Zhang B, Jarosinski MC, Ransier A, Chenine AL, Asokan M, Bailer RT, Bose M, Cagigi A, Cale EM, Chuang GY, Darko S, Driscoll JI, Druz A, Gorman J, Laboune F, Louder MK, McKee K, Mendez L, Moody MA, O'Sullivan AM, Owen C, Peng D, Rawi R, Sanders-Buell E, Shen CH, Shiakolas AR, Stephens T, Tsybovsky Y, Tucker C, Verardi R, Wang K, Zhou J, Zhou T, Georgiou G, Alam SM, Haynes BF, Rolland M, Matyas GR, Polonis VR, McDermott AB, Douek DC, Shapiro L, Tovanabutra S, Michael NL, Mascola JR, Robb ML, Kwong PD, Doria-Rose NA. Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual. Immunity. 2019 Mar 19;50(3):677-691.e13.
Schramm CA, Douek DC. Beyond Hot Spots: Biases in Antibody Somatic Hypermutation and Implications for Vaccine Design. Front Immunol. 2018 Aug 14;9:1876.
- Single cell RNASeq and CITEseq analysis of innate and adaptive immune responses
- Dynamics of IG and TR repertoires in response to vaccination and infection
- Somatic hypermutation and antibody phylogenetics
- Impact of IG genetics on immune outcomes
Leadership Transition at the NIAID Vaccine Research Center
I extend my heartfelt gratitude and deepest respect to John R. Mascola, M.D., as he announces his retirement as Director of the Dale and Betty Bumpers Vaccine Research Center at the National Institute of Allergy and Infectious Diseases. Dr. Mascola will leave NIAID at the end of March.
Contact
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Contact the NIAID News & Science Writing Branch.
VRC Clinical Trial Publications
The Vaccine Research Center (VRC) Clinical Trials Program evaluates investigational vaccines and monoclonal antibodies (mAb) in clinical studies. Data generated from the safety and immunogenicity assessments are analyzed and presented in study publications. Below is a listing of recent publications of VRC clinical trials.
Experimental mRNA HIV Vaccine Safe, Shows Promise in Animals
An experimental HIV vaccine based on mRNA—the same platform technology used in two highly effective COVID-19 vaccines—shows promise in mice and non-human primates, according to scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Their results, published in Nature Medicine, show that the novel vaccine was safe and prompted desired antibody and cellular immune responses against an HIV-like virus.
Contact
Submit a Media Request
Contact the NIAID News & Science Writing Branch.
Human Immune Response to Ixodes Scapularis Tick Bites
Contact Information
Office: 301-435-7244
Phone: 301-435-7244
Email: LymeDxStudies@niaid.nih.gov
Hours: Monday-Friday, 8:00 a.m. to 4:00 p.m.
Vaccine Research Center Senior Leadership
Online Survey About Eczema
This 10- to 20-minute survey is available for patients with eczema or parents of patients with eczema. These questions will help us learn more about patient experiences to improve current research and guide future research.
What does the study involve?
This online survey involves 10 to 20 minutes’ worth of questions.
Who Can Participate?
Adults with eczema or parents/caregivers of a child with eczema.
Where Is It Taking Place?
This survey takes place online.
Is There a Cost?
No
Is Compensation Provided?
No
Contact Information
Office: Epithelial Therapeutics Unit
Phone: 301-451-8860
Email: Ashleigh.Sun@NIH.gov
Monoclonal Antibody Prevents Malaria in Small NIH Trial
One dose of a new monoclonal antibody discovered and developed at the National Institutes of Health safely prevented malaria for up to nine months in people who were exposed to the malaria parasite. The small, carefully monitored clinical trial is the first to demonstrate that a monoclonal antibody can prevent malaria in people. The trial was sponsored and conducted by scientists from the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, and was funded by NIAID.
Contact
Submit a Media Request
Contact the NIAID News & Science Writing Branch.
NIH Launches Clinical Trial of Universal Influenza Vaccine Candidate
A first-in-human, Phase 1 trial assessing the safety and immunogenicity of an investigational nanoparticle influenza vaccine designed to provide long-lasting protection against multiple flu virus strains has begun at the National Institutes of Health Clinical Center in Bethesda, Maryland. Healthy participants 18 to 50 years old will receive either a licensed seasonal influenza vaccine or the experimental vaccine, FluMos-v1.
Contact
Submit a Media Request
Contact the NIAID News & Science Writing Branch.