Medical College of Wisconsin Infectious Diseases Research
The division is involved in multidisciplinary research including bench and translational research, clinical trials, and behavioral trials. Collaborative research efforts are ongoing with internal and external partners. MCW faculty are engaged in a variety of clinical research trials conducted in collaboration with research networks and industry sponsored-trials. Faculty also practice at the AIDS Resource Center of Wisconsin and are able to offer most of the clinical trials through that location as well.
Dr. Sol Aldrete's clinical and research interests focus on HIV care, from counseling and prevention to immunologic response and treatment. In the past, I focused my research on HIV immune non-responders (INR) and finding a CD4 recovery pattern most predictive of long-term outcomes and mortality. I am currently looking at the clinical characteristics and outcomes of COVID-19 infection in people living with HIV.
Research in the Coburn laboratory focus on pathogenic spirochetes, a group of bacteria that are able to cause persistent, disseminated infections in immunocompetent animals, including humans. We are currently working with Borrelia burgdorferi, which is maintained in a tick-animal cycle in nature. We also work with another pathogenic spirochete, Leptospira interrogans. Leptospires are maintained in infected animals in nature, but can also survive in water and mud. Since both pathogens are maintained in animal reservoirs in nature, both are referred to as zoonotic infections. The focus of our work with both Borrelia and Leptospira is to identify and then test the biologic significance of bacterial proteins that help the bacteria bind to mammalian cell surface receptors, to identify the mammalian cell surface receptors recognized by the bacteria, and ultimately the biological and pathologic significance of the interaction between the bacterial protein and the mammalian receptor.
In the Borrelia work, we have two main projects ongoing in the lab. In one, we are trying to understand the mechanisms behind the requirement for the B. burgdorferi protein, P66, for the bacteria to cause infection in mammals. P66 binds to mammalian cell surface receptors called integrins and serves as a porin in the bacterial outer membrane. We know that the integrin binding function is important for the bacteria to cross the endothelial layers that line the vascular system and disseminate to different sites in the body. In another Borrelia project, we developed a new experimental model to determine the roles of bacterial adhesive proteins in how the bacteria interact with endothelial cells to colonize different tissues in mammals, and how they survive the mammalian defenses in the bloodstream.
In the Leptospira work, we also focus on how the bacteria interact with endothelial cells. In severe cases of leptospirosis, widespread endothelial damage is seen, and this is associated with hemorrhage. L. interrogans binds to an endothelial cell surface receptor called VE-cadherin, which helps the endothelial cells form cell-cell junctions that maintain the integrity of small blood vessels. We are currently determining how the bacteria disrupt cadherin-cadherin interactions, and determining whether the bacterial proteins that bind VE-cadherin are responsible for the endothelial disruption caused by the bacteria. In a second Leptospira project, we are working to identify the bacterial proteins that help the bacteria bind to the endothelial layer to promote bacterial association with the kidney, where the bacteria reside in a chronically infected animal and from where they are released into the environment.
Dr. Carlos Figueroa Castro’s research includes non-tuberculous mycobacterial infections, including refractory infections. He has large datasets analysis for observational research.
Dr. Michael Frank conducts clinical trials, primarily of new treatments in management of HIV infection. This includes long-term multicenter trials funded by NIH through collaborative networks, such as the START trial through the INSIGHT network, and the REPRIEVE trial through the AIDS Clinical Trials Group, as well as industry-sponsored clinical trials including those of new long-acting injectable treatments for HIV. He is also site principal investigator for clinical trials of treatments and vaccination for other infections, including Lyme, mycobacterial, and fungal infections. He also participates in medical education research.
Dr. Mary Beth Graham’s research includes Clinical trials COVID therapeutics. Her Past Trials are Gilead – Remdesivir Expanded Access Program (Site PI); Merck – Phase 2/3 Molnupiravir in outpatients with COVID (Site PI). Her upcoming trials are Regeneron – Regeneron’s investigational antibody treatment (2237) of COVID-19 in immunocompromised patients with persistent COVID-19; HIV therapeutics: Co-investigator in HIV trials ongoing in Infectious Diseases clinic; Bacteriophage therapy: Co-Investigator for upcoming trial (Phase 1b/2a) looking at efficacy of bacteriophages in treatment of Staphylococcus aureus bacteremia; and Quality Improvement: Efforts related to reduction of hospital acquired infections and identification of multidrug resistant organisms – QI projects related to my role as the Medical Director of Infection Prevention and Control for Froedtert Hospital.
Dr. Michael Kron is a professor with tenure at Froedtert & the Medical College of Wisconsin Division of Infectious Diseases since 2005. He attended Northwestern University Feinberg School of Medicine in Chicago and completed his internal medicine residency also in Chicago at Northwestern Memorial Hospital. Following residency he received a Master’s Degree in Clinical Tropical Medicine at the London School of Hygiene and Tropical Medicine, University of London. He then returned to the USA and completed research and clinical fellowships in Infectious Diseases and Geographic Medicine (Tropical Medicine) at Case Western Reserve University and University Hospitals in Cleveland, OH. Dr. Kron has maintained his interests in Clinical Tropical Medicine through collaborations with institutions in Asia, Africa, and South America. His research interests are in general infectious diseases, molecular microbiology and diagnostic testing, international health, tropical medicine and parasitology. His collaborative research in Neglected Tropical Diseases includes drug discovery from natural products for improved treatment of lymphatic filariasis and schistosomiasis, and structure-function relationships among the parasite enzymes known as tRNA synthetases with multiple biological activities. He is also interested in education and curriculum improvement with organizations in developing countries.
Dr. Keith Woeltje's research interests are in clinical decision support and the use of electronic data for surveillance of healthcare associated infections and other adverse events.