The Genetics of Tuberculosis Resistance

Dr. Cathy Stein and her Ugandan research team

Dr. Cathy Stein is a genetic epidemiologist who studies the molecular mechanisms that underly resistance to Mycobacterium tuberculosis.  In collaboration with Drs. Scott Williams and Henry Boom, Dr. Stein is conducting a study in Uganda to examine individuals that are presumed resistant to M. tuberculosis infection, also called RSTRs. These individuals demonstrate persistently negative tuberculin skin tests and blood-based tests several years after close and sustained exposure to an infectious TB case in a TB-endemic setting.  These individuals do not appear different from latently infected individuals with respect to other known risk factors for TB infection (see Ma et al. 2014, BMC Infectious Diseases for more details). Genetic and transcriptomic studies of this phenotype have revealed novel genes and pathways associated with RSTR, and larger validation studies are ongoing.

Dr. Stein also studies HIV-infected individuals that do not develop active TB disease despite being immunosuppressed and living in a highly-exposed, TB-endemic household setting.  Dr. Stein and colleagues have recently published a genome-wide association study showing theIL12B gene as a strongly protective gene against TB (Sobota et al. 2016, Am J Hum Genet).

Dr. Stein’s work on tuberculosis resistance is funded by 2 NIH grants and a research grant from the Bill & Melinda Gates foundation.


Sobota RS, Stein CM, Kodaman N, Scheinfeldt LB, Maro I, Wieland-Alter W, Igo RP Jr, Magohe A, Malone LL, Chervenak K, Hall NB, Modongo C, Zetola N, Matee M, Joloba M, Froment A, Nyambo TB, Moore JH, Scott WK, Lahey T, Boom WH, von Reyn CF, Tishkoff SA, Sirugo G, Williams SM.  A Locus at 5q33.3 Confers Resistance to Tuberculosis in Highly Susceptible Individuals. Am J Hum Genet. 2016 Mar 3;98(3):514-24

Ma N, Zalwango S, Malone LL, Nsereko M, Wampande EM, Thiel BA, Okware B, Igo RP Jr, Joloba ML, Mupere E, Mayanja-Kizza H, Boom WH, Stein CM;Tuberculosis Research Unit (TBRU).  Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda.  BMC Infect Dis. 2014 Jun 27;14:352.