Ruben Martinez Barricarte, Ph.D.

Ruben
Martinez
Barricarte, Ph.D.
Assistant Professor of Medicine, Division of Genetics
Assistant Professor of Pathology, Microbiology and Immunology

Inborn errors of immunity (IEIs) are a heterogeneous group of monogenic diseases that cause impaired development or function of the immune system. Historically, IEIs were considered diseases that lead to susceptibility to severe infections. David Vetter (aka the bubble boy), the most mediatic case of these diseases, was born with an IEI that causes the absence of T and NK cells and, consequently, susceptibility to multiple severe infections. Interestingly, in the past few years, the clinical spectrum of patients with IEIs has expanded to encompass other clinical manifestations such as autoimmunity, allergy, autoinflammation, or cancer. Nowadays, there are about 500 known genetic causes of IEIs, and their study is instrumental in providing a genetic diagnosis for patients, counseling for families, and applying preventive treatments for individuals at risk. Furthermore, these patients, often “knockouts” of specific molecules, provide a unique opportunity to understand the mechanisms of human immunity without relying on artificial models. However, despite all the advances in the field, about half of the patients with a suspected IEI of immunity lack a genetic diagnosis, and in a sizeable fraction of patients with genetically diagnosed IEIs, the pathological molecular mechanisms of the mutations remain elusive. Furthermore, despite compelling evidence that a single gene mutation can cause severe infections by a specific pathogen, most infectious diseases have not been studied as IEIs. Through an international network of collaborators, our lab recruits and studies patients with IEIs of unknown genetic etiology, patients with genetically defined IEIs of unknown molecular mechanism, and patients with selective susceptibility to specific infectious agents. Using next-generation sequencing, we identify new genetic causes of IEIs. Furthermore, employing a multidisciplinary approach combining molecular biology, biochemistry, human immunology, computational biology, and multi-omics, we functionally characterize the mutations responsible for the diseases in our patients. Finally, our lab leverages the basic molecular, immunological and biological insights from studying these patients to develop new immunomodulatory approaches for common diseases like cancer.

Publications on PubMed.gov

Phone
(615) 936-2660
ruben.m.barricarte@vumc.org

Human immunology, human genetics, infectious diseases, molecular biology, primary immunodeficiencies (PID), immunogenetics

Romney M. Humphries, Ph.D., D(ABMM), M(ASCP)

Romney
Humphries, Ph.D., D(ABMM), M(ASCP)
Professor of Pathology, Microbiology, and Immunology
Medical Director of the Microbiology Laboratory

Antimicrobial resistance (AMR) is one of the most pressing concerns in infectious diseases, if not all of medicine. A major dilemma in this scenario is the technologies relied to detect AMR infections are based on methods developed a century ago. More accurate and rapid methods are needed to curtail the spread of AMR and also improve patient outcomes. The Humphries laboratory evaluates methods that improve the speed and accuracy of identifying antibiotic-resistant bacteria infecting patients along with the impact such improved technologies may have on patient care. Additionally, our laboratory investigates novel AMR mechanisms in clinical bacterial isolates as they evolve in real time, and novel antimicrobials designed to treat these infections.

Publications on PubMed.gov

romney.humphries@vumc.org

Antimicrobial resistance, Bacterial pathogenesis, Diagnostic testing, Clinical microbiology

Wenhan Zhu Ph.D.

Wenhan
Zhu Ph.D.
Assistant Professor of Pathology, Microbiology, and Immunology
Phone
615-875-1271
Office Address
1161 21st Avenue South
Medical Center North
Room / Suite
U-2215 MCN
Nashville
Tennessee
37232

In our lab, we focus on the metabolic interactions that dictate the changes or resilience of the microbiota. Insight into such interactions would enable precise manipulation of gut microbiota composition, thus restoring a balanced community in situ and improving host health. To precisely manipulate the microbiota, we use a multidisciplinary discovery pipeline that consists of next-generation sequencing, bacterial genetics and a mechanistic understanding of bacterial physiology in vivo. This pipeline allows us to discover druggable targets of the microbiota and translate our finding using high-throughput screening.

Publications on PubMed.gov

wenhan.zhu@vumc.org

Resilience mechanism of gut commensals, metabolic targeting of gut microbes to promote commensal resilience, and the roles of bacterial toxin in promoting colorectal cancer development

Antibody Therapy vs. Vaccine

Vaccines and antibody therapeutics are two of the most promising measures to counteract SARS-CoV-2, and subsequent COVID-19 disease. While there is some overlap between these two approaches, there are some key distinctions to be drawn... Click the graphic to the left to learn the basics!

Spotlight: Crowe Lab

Members of the Vanderbilt Institute for Infection, Immunology and Inflammation are making extraordinary advances in health and medicine. VI4 is developing therapies for the treatment of infection, autoimmunity, and cancer. At the frontline of the COVID-19 pandemic is the laboratory of VI4 member, Dr. James Crowe.... Click the image on the left to continue reading.

Faculty Spotlight: Carlos Henrique Serezani, Ph.D.

Dr. Serezani completed his PhD at the University of Sao Paulo and the University of Michigan. He also completed his postdoctoral studies at University of Michigan. He was an Assistant Professor at Indiana University School of Medicine and has published more than 50 papers in reputed journals. The NIH and other foundations have funded his laboratory for almost 10 years. The Serezani laboratory aims to develop therapeutic strategies to control systemic (sepsis) and localized infections (skin and lung) in healthy individuals, individuals with immune deficiencies, and those suffering from chronic inflammatory diseases, such as diabetes. They have concentrated much of their efforts in understanding the role of the lipid mediators leukotriene B4 and prostaglandin E2 and their actions on microRNAs, epigenetic changes and phosphatases to modulate immune cells involved in the control of microbial infection in these different contexts..... Click Dr. Serezani's photo to continue reading.

Faculty Spotlight: Justin M. Balko, Pharm.D., Ph.D.

Justin M. Balko, Pharm.D., Ph.D. is an Associate Professor of Medicine, Cancer Biology and Pathology, Microbiology and Immunology. He received his Pharm.D. from State University of New York at Buffalo and his Ph.D. from the University of Kentucky, Department of Pharmaceutical Sciences. Balko's laboratory is focused on improving treatment outcomes in breast cancer (particularly triple-negative breast cancer) as well as in other solid tumors. To accomplish this, they integrate data from genomic and molecular profiling studies with molecular biology and signal transduction methodologies to translationally identify altered pathways in cancer, the functional consequences of these alterations, and ways to directly target them in patients to improve clinical outcomes and survival. These efforts span in silico (publically available databases), in vitro (cell culture), in vivo (mouse and human clinical studies) and in situ (histology) methods. The lab has a strong interest in the intersection between new immunotherapies and tumor cell signaling pathways.... Click Dr. Balko's photo to continue reading.