Tuberculosis remains a serious threat to global health. The development of transformational new interventions for this disease relies on understanding the fundamental biology that determines the pathogenesis of the disease. We are a diverse group of bacteriologists, immunologists, and geneticists that are focused on understanding the critical interactions between Mycobacterium tuberculosis and its human host that determine disease progression and treatment response.
Bacterial growth and division during M.tuberculosis infection is poorly understood. A clear picture of the mechanisms utilized for bacterial growth during the progression of infectious disease will advance our understanding of bacteria survival during exposure to various stresses. Christina uses a variety of approaches incorporating quantitative imaging to investigate mycobacterial growth patterns in vitro and in vivo. Christina received her PhD from the University of California Berkeley in the lab of Dr. Tom Alber where she studied the M.tuberculosis serine/threonine kinase response network.
Energy generating metabolic processes like oxidative phosphorylation lead to the production of noxious reactive oxygen species that damage DNA. Using a dual transcriptomic - metabolomic approach, Aditya is interested in uncovering mechanisms that M tuberculosis might use to protect its replicating DNA from the chemically reactive by-products of oxidative metabolism. Aditya received his M.Sc. in Microbiology at the Maharaja Sayajirao University of Baroda, India where examined the potential of soil bacteria and actinomycetes to act as biocontrol agents against the plant disease, fusarial wilt.
Michelle is interested in understanding the mechanisms that control antibiotic efficacy in Mycobacterium tuberculosis (Mtb). Tuberculosis control is limited by the length of antibiotic treatment needed to prevent recurrent disease. A factor contributing to the relative inefficacy of antibiotics appears to be the drug-tolerant state that is assumed by Mtb during infection. Michelle’s work focuses using bacterial genetics to understand drug efficacy during infection.
While about 80% of the genome is transcribed, only 1% of the genome is protein-coding and the function of most non-coding transcripts remain unknown. A member of the MD-PhD program at UMass, Mike joined the Sassetti lab in the fall of 2015 to study the immunomodulatory role of long non-coding RNAs. Mike uses both in vitro and in vivo approaches to probe the function of long non-coding RNAs in the setting of Mycobacterium tuberculosis infection. A graduate of Georgetown University, he received his B.Sc in the Biology of Global Health.
Mycobacterium tuberculosis encounter numerous microenvironments within the host with varying nutrient availability as well as host mediated stress factors. Investigating the mechanisms of essential metabolic pathways in these microenvironments will help identify targets for novel therapeutic approaches. Eun-Ik is interested in utilizing bacterial genetics and mass spectrometric approaches to investigate essential pathways of Mtb nutrient acquisition and metabolism. Eun-Ik received his PhD from Washington University in St. Louis in the laboratory of Dr. Jeffrey Henderson, where he investigated metal acquisition by the yersiniabactin metallophore system in uropathogenic E. coli.
Granulocytic inflammation within the lungs is a major immunological determinant of tuberculosis disease progression. The massive influx of neutrophils into the pulmonary compartment is a hallmark of progressive tuberculosis, and it has recently become clear that neutrophilia is not just a consequence of infection, but is also driving disease. Rustin uses multiple in vivo mouse models to understand how neutrophils impact both the host immune regulatory network and the bacterial microenvironment in quiescent verses active infection states. Rustin received his PhD from the Geisel School of Medicine at Dartmouth College in the lab of Dr. Brent Berwin, where he studied immune response mechanisms to Pseudomonas aeruginosa motility.
It is becoming increasingly clear that survival during M. tuberculosis infection depends on two distinct immune mechanisms: "resistance" to pathogen replication, and "tolerance" of the tissue damage caused by the persistent pathogen and the subsequent inflammatory immune response. Andrew uses in vivo models of resistance and tolerance in combination with global host and bacterial genetic approaches to identify immune mechanisms that prevent disease progression and might be targeted to overcome pathogen virulence strategies. Andrew received his PhD from Harvard Medical School in the lab of Dr. Michael Starnbach where he examined T cell responses and host-pathogen interactions during chronic infections with Chlamydia trachomatis.
Yao’s research deals with how genetic diversity affects macrophage immune responses to M. tuberculosis infection in vitro. He employs a combination of techniques including fluorescent reporter bacteria, flow cytometry, microscopy, and RNA sequencing to understand macrophage function and bacterial responses. The overarching goal is to elucidate how population genetic diversity affects disease susceptibility. He received his BA from the University of Cambridge and completed his doctoral training from the University of Pittsburgh working on the non-human primate model of tuberculosis.
Genetic variation in the host and pathogen underlie outcome to infection. Clare has developed a “dual-genome” system to understand the host and bacterial genetic determinants of susceptibility to infection, the host genotype-specific preferential growth of different lineages of Mtb and the mechanisms of vaccine protection in diverse hosts. Clare received her PhD from the Menzies Research Institute in Australia in the lab of Prof Simon Foote, where she identified host genes required for growth of the malarial parasite and targeted these pathways as novel host-directed therapeutics.