Charles Laboratory: Richelle C. Charles, MD, FIDSA

Overview

The Richelle C. Charles, MD, FIDSA, Laboratory at Massachusetts General Hospital is focused on evaluating host-pathogen interactions and immune responses to enteric pathogens with the goal to improve vaccination strategies and diagnostics for diarrheal diseases.

Diarrheal diseases remain the third leading cause of death in low income countries that lack access to safe drinking water and improved sanitation; they are the fifth leading cause of death worldwide.

Diarrheal episodes reduce productivity at the community level and contribute to intestinal barrier dysfunction, which perpetuates a cycle of malnutrition, infection, disease and poverty.

The Charles Lab at Massachusetts General Hospital Infectious Diseases Division is committed to making scientific contributions that will put a wrench in this cycle. Our research is focused on furthering our understanding of host-pathogen and immune responses to Vibrio cholerae (the cause of cholera) and Salmonella enterica serovar Typhi and Paratyphi A (the cause of typhoid/paratyphoid fever).

The Charles lab has multiple collaborative studies in Bangladesh, Nepal and Haiti. Specifically, our projects focus on using high-throughput proteomic and genomic platform technologies to identify immunogenic antigens for vaccine and diagnostic development for these intestinal infections.

Research Projects

Development of Improved Diagnostics for Acute and Chronic Salmonella Infections

Collaborators:
Firdausi Qadri, PhD, International Centre for Diarrhoeal Diseases Research, Dhaka, Bangladesh
Jason Andrews, MD Stanford University School of Medicine
Bala Ram Malla, MD, and Rajeev Shrestha, Dhulikhel Hospital Kathmandu University Hospital, Nepal
Edward T. Ryan, MD, Massachusetts General Hospital
Galit Alter, PhD, Ragon Institute of MGH, MIT, and Harvard

Investigating the Adaptive Mechanisms Used by Salmonella to Evade the Immune System and Persist in the Biliary Tract of Asymptomatic Chronic Carriers of S. Typhi and Paratyphi A

Collaborator:
John Gunn, PhD, Ohio State University

Characterizing the Antigenic Targets and Functional Characteristics of Protective Antibodies Against Cholera

Collaborators:
Jason B. Harris, MD, MPH, Massachusetts General Hospital
Firdausi Qadri, PhD, International Centre for Diarrhoeal Diseases Research, Dhaka, Bangladesh
Galit Alter, PhD, Ragon Institute of MGH, MIT, and Harvard
Phil Felgner, PhD, University of California, Irvine

Lab Members

Richelle C. Charles, MD, FIDSA
Principal Investigator in the Division of Infectious Diseases, Massachusetts General Hospital
Assistant Professor of Medicine, Harvard Medical School

Richelle C. Charles, MD, FIDSA, is a physician-investigator with funding from the National Institutes of Health and the Bill and Melinda Gates Foundation. She has over 40 publications in peer-reviewed journals. Dr. Charles received her MD degree from the Johns Hopkins University School of Medicine, completed her residency in internal medicine at the Massachusetts General Hospital, and completed the clinical infectious disease fellowship in the Infectious Disease Fellowship training program of Mass General and the Brigham and Women’s Hospital. Dr. Charles is certified by the American Board of Internal Medicine in general internal medicine and infectious diseases.

Dr. Charles has experience working in multicenter collaborative efforts with investigators from the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Partners In Health, Stanford University, and Mass General - Harvard that focus on broadening our understanding of host-pathogen and immune responses during human infection by Vibrio cholerae and Salmonella enterica serovar Typhi and Paratyphi A (the primary causes of enteric fever). Her primary research focus is on the: 1) application of high-throughput proteomic and genomic platform technologies to identify immunogenic antigens for vaccine and diagnostic development for these infections, 2) development of diagnostics for S. Typhi and Paratyphi A infection, and 3) characterization of immune responses during human infection and vaccination with enteric infections.

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Ariana Nodoushani
Research Technician

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Meti Debela
Research Technician

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International Research Collaborations/Teams

International Centre for Diarrhoeal Disease Research, Bangladesh

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Dhulikhel Hospital/Kathmandu Medical College & Teaching Hospital Nepal

Publications

Selected Publications

1. Andrews JR, Qamar FN, Charles RC, ET Ryan. Extensively drug-resistant typhoid - Are conjugate vaccines arriving in time? N Engl J Med. 2018;379(16):1493-1495. PMID:30332569
2. Andrews JR, Khanam F, Rahman N, Hossain M, Bogoch II, Vaidya K, Kelly M, Calderwood SB, Bhuiyan TR, Ryan ET, Qadri F, Charles RC. Plasma IgA responses against two Salmonella Typhi antigens identify patients with typhoid fever. Clin Infect Dis..2019;68(6):949-955. PMID:30020426.
3. Park KS, Kim H, Kim S, Lee K, Park S, Song J, Min C, Khanam F, Rashu R, Bhuiyan TR, Ryan ET, Qadri F, Weissleder R, Cheon J, Charles RC, Lee H. Nanomagnetic system for rapid diagnosis of acute infection. ACS Nano. 2017;11:11425-11432. PMID: 29121461
4. Charles RC, Nakajima R, Liang L, Jasinskas A, Berger A, Leung DT, Kelly M, Xu P, Kováč P, Giffen SR, Harbison JD, Chowdhury F, Khan AI, Calderwood SB, Bhuiyan TR, Harris JB, Felgner PL, Qadri F, Ryan ET. The plasma and mucosal IgM, IgA, and IgG responses to the Vibrio cholerae O1 protein immunome in adults with cholera in Bangladesh. J Infect Dis. 2017; 216(1):125-134. PMID: 28535267.
5. Kauffman RC, Bhuiyan TR, Nakajima R, Mayo-Smith LM, Rashu R, Hoq MR, Chowdhury F, Khan AI, Rahman A, Bhaumik SK, Harris L, O'Neal JT, Trost JF, Alam NH, Jasinskas A, Dotsey E, Kelly M, Charles RC, Xu P, Kováč P, Calderwood SB, Ryan ET, Felgner PL, Qadri F, Wrammert J, Harris JB. Single-cell analysis of the plasmablast response to Vibrio cholerae demonstrates expansion of cross-reactive memory B cells. mBio. 2017; 7(6). PMID: 27999163
6. Charles RC, Hilaire IJ, Mayo-Smith LM, Teng JE, Jerome JG, Franke M, Saha A, Yu Y, Kováč P, Calderwood SB, Ryan ET, LaRocque RC, Amazor CP, Qadri F, Ivers LC, Harris JB. Immunogenicity of a Killed Bivalent (01 and 0139) Whole cell oral cholera vaccine, Shanchol^®, in Haiti. PLoS Negl Trop Dis. 2014; 8(5):e2828. PMID:247886645.
7. Park KS, Chung HJ, Khanam F, Lee H, Rashu R, Bhuiyan MT, Berger A, Harris JB, Calderwood SB, Ryan ET, Qadri F, Weissleder R, Charles RC.  A magneto-DNA nanoparticle system for the rapid and sensitive diagnosis of enteric fever.  Sci Rep. 2016; 6:32878. PMID:27605393
8. Charles RC, Sultana T, Alam MM, Yu Y, Wu-Freeman Y, Bufano MK, Rollins SM, Tsai L, Harris JB, Larocque RC, Leung DT, Brooks WA, Nga TV, Dongol S, Basnyat B, Calderwood SB, Farrar J, Khanam F, Gunn JS, Qadri F, Baker S, Ryan ET. Identification of immunogenic Salmonella enterica serotype Typhi antigens expressed in chronic biliary carriers of Typhi in Kathmandu, Nepal. PLoS Negl Trop Dis. 2013; 7(8):e2335. PMID: 23936575.
9. Charles RC, Liang L, Khanam F, Sayeed MA, Hung C, Leung DT, Baker S, Ludwig A, Harris JB, Larocque RC, Calderwood SB, Qadri F, Felgner PL, Ryan ET. Immunoproteomic analysis of antibody-in-lymphocyte supernatant (ALS) in patients with typhoid fever in Bangladesh. Clin Vaccine Immunol. 2013; 21(3):280-5. PMID: 24371257.

Full list of Dr. Charles publications