Medical College of Wisconsin Infectious Diseases Research

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.

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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.

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Dr. Figueroa Castro's projects include research on COVID-19 infection and its impact on patients with non-tuberculous Mycobacterium infections by the use of National COVID Cohort Collaborative (N3C), a partnership among the National Center for Advancing Translational Sciences (NCATS), the National Center for Data to Health (CD2H), and National Institute of General Medical Sciences–funded Institutional Development Award (IDeA) Program Networks for Clinical and Translational Research (IDeA-CTR) networks. In collaboration with the Clinical and Translational Science Institute of Southeastern Wisconsin, access to N3C datasets by other researchers at MCW have allowed additional research on the impact of COVID-19 infection in various population of interest in general surgery, perioperative medicine, and stem cell transplant. He is the site principal investigator for various multicenter clinical trials to study compounds against refractory non-tuberculous Mycobacterium infections including Lamprene Multiple Patient Program (clinicaltrials.gov ID NCT04334070), and Study of Epetraborole in Patients With Treatment-refractory MAC Lung Disease (clinicaltrials.gov ID NCT05327803). He has published articles in infection prevention including the impact of Clostridioides difficile reporting after changes in diagnostic workflows, and the clinical description of patients affected by Elizabethkingia infection, a multistate outbreak.

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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 INSIGHT network and the AIDS Clinical Trials Group, as well as industry-sponsored clinical trials. The focus of active clinical trials includes new immune-mediated mechanisms of controlling HIV without antiviral drugs. He is also site principal or co-investigator for clinical trials of treatments for other infections, including viral, mycobacterial, and fungal infections. He also participates in medical education research.

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Dr. Mary Beth Graham’s research includes Clinical trials and Quality Improvement. She has been the site PI on several clinical trials focusing on COVID therapeutics including Gilead – Remdesivir Expanded Access Program (Site PI); Merck – Phase 2/3 Molnupiravir in outpatients with COVID (Site PI), and the FDA expanded access program for convalescent plasma in the treatment of patients with COVID-19. She is currently the site PI for the Strategies and Treatments for Respiratory Infections and Viral Emergencies (STRIVE) clinical trial. STRIVE is a group of research studies to investigated drugs and treatment strategies for adults in the hospital with respiratory or lung infection (Strategies and Treatments for Respiratory Infections and Viral Emergencies (STRIVE) | NIAID: National Institute of Allergy and Infectious Diseases (nih.gov). That trial is currently studying an investigational antiviral drug, ensitrelvir, in the treatment of hospitalized patients with COVID-19. She is currently a co-investigator on several HIV therapeutics trials ongoing in the Froedtert Hospital Infectious Diseases clinic and a Bacteriophage therapy: Phase 1b/2a trial looking at efficacy of bacteriophages in treatment of Staphylococcus aureus bacteremia. As the Medical Director of Infection Prevention and Control for Froedtert Hospital she is involved in ongoing quality Improvement efforts related to reduction of hospital acquired infections and identification of multidrug resistant organisms.

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Dr. Jack Keegan’s research focuses on quality improvement in the multidisciplinary management of endocarditis, HIV prevention in high-risk populations, and harm reduction in persons who inject drugs. Current projects include a community embedded telehealth service for HIV pre-exposure prophylaxis in women who do sex work, and a hospital-based program to increase the usage of medications for opioid use disorder in patients with serious injection related infections.

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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.

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The Surdel Laboratory focuses on pathogenic Leptospira species, which are gram-negative spirochetes and the causative agents of leptospirosis. Leptospirosis is a potentially fatal zoonosis that disproportionately affects resource-poor parts of the world. The goal of the Surdel Laboratory is to identify and define the mechanisms that pathogenic bacteria utilize to bind host cells and ligands. This work will provide novel insight into the ability of Leptospira to colonize and cause disease within the host, and ultimately help guide the development of novel therapeutics and vaccines.

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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.

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