Immunology and Translational Research
The immune system is a complex collection of cells and organs that actively survey our bodies for pathogens and damaged cells to protect us against disease. Current immunology research by investigators in the Drexel MIIM graduate program focuses on dendritic cell — the most potent antigen-presenting cells — biology, functions and immunotherapeutic potential against human chronic viral infections and neuroinflammatory diseases, understanding antitumor immune responses and the development of novel therapeutics, and neonatal immunity to viral infections.
Our immune system begins developing before birth and continues to evolve throughout our lifetime. One area of active research within the program is focused on understanding why newborns, particularly preterm infants, are more susceptible to respiratory viral infections. Studies involve addressing how innate and adaptive immune responses evolve during the first few months of life and testing novel approaches to boost immunity in the neonatal lung environment.
Several research groups are studying how viruses interact with and subvert host immunity or drive dysfunctional immune responses to pathogens such as HIV, HTLV-1, COVID-19 or model systems of chronic virus infection. Specific interests include studying how viral and host factors contribute to neuroinflammation and affect dendritic cell function, addressing how features of immune aging or immunosenescence may contribute to decreased vaccine responsiveness, and how different vaccine platforms promote different responses in antigen-presenting cells. Translationally focused studies in the department leverage our understanding of host-pathogen interactions to develop vaccines or immunotherapies to enhance cellular and humoral immunity or overcome immune defects.
Another connected area of research is focused on understanding antitumor immune responses and understanding how chronic antigen exposure and the suppressive tumor microenvironment limit effective antitumor immunity. Current cancer immunology research in the department seeks to understand what drives effective versus ineffective antitumor immunity so that this knowledge can be used to develop immunotherapies such as novel immune checkpoint inhibitors that promote better responses in individuals with cancer.
Our immune system provides vital protection against pathogens and disease, but when something goes wrong it can lead to autoimmunity. Autoimmune diseases affect an estimated 14 to 22 million Americans. Current autoimmunity research within the MIIM program is focused on three major autoimmune disorders: scleroderma, rheumatoid arthritis and multiple sclerosis. Major efforts have focused on investigating the initiation of scleroderma, which has led to the design of translational novel therapeutics controlling extracellular matrix synthesis and thus regulating the fibrotic pathology of this disease.
Malaria
Malaria remains a major health problem in a large part of the world, with 250 million cases and 600,000 deaths per year. With about 30 researchers consisting of faculty, postdoctoral fellows, students and technicians, research on the parasite that causes malaria is a major area of research emphasis in the Microbiology and Immunology graduate program. The range of research interests includes basic molecular and cell biological studies, understanding the mechanisms of antimalarial drug action and resistance, studying immunity to malaria and vaccine development, field studies in Africa and Asia using genetic epidemiology of malaria, and discovery and development of new antimalarial drugs. A wide range of state-of-the-art tools and approaches are used in these studies. These include CRISPR-Cas9 genome modification of parasites, mRNA vaccine development, whole genome sequencing and bioinformatics, molecular dynamics and modeling, antimalarial drug designs, and cryo-electron microscopy/tomography. Researchers at the College of Medicine are supported by multiple grants from the National Institutes of Health.
Bacterial Pathogenesis, Genomics, Metabolism and Drug Discovery
Bacterial infections cause enormous worldwide disease burden that is quickly growing with rising antibiotic resistance. The extremely high diversity of species in the bacterial kingdom and the rapid rates they evolve present major challenges to developing new therapies to combat infections, especially chronic and recurrent infections. Investigators in the Drexel MIIM graduate program broadly investigate mechanisms of chronic bacterial disease and devise new approaches to diagnosis and treatment. They apply evolutionary genomics, metabolic profiling, genetic engineering, vaccine development and designer drug discovery, in order to understand how bacteria cause persistent infections, especially in the context of bacterial biofilms and antibiotic resistance.
Current research focuses on identifying new virulence factors through comparing the genomes of clinical isolates from natural history collections, defining and manipulating secondary metabolism pathways, and developing inhibitors to block the ability of dormant bacteria to tolerate antibiotics. Related work involves developing new technologies to profile microbiomes through genomic sequencing, pan-transcriptome analysis and metabolomic profiling. Investigators in the College of Medicine are highly collaborative and work in a variety of model systems, including active collaborations investigating middle ear infections, wound infections, chronic obstructive pulmonary disease, cystic fibrosis, diarrheal diseases, sepsis and Alzheimer’s disease. Several species investigated are associated with mucosal infections as opportunistic pathogens, like Haemophilus influenzae, Clostridioides difficile, Vibrio cholerae, Pseudomonas aeruginosa, Staphylococcus aureus, non-tuberculous Mycobacteria, Enterococcus and Escherichia coli.
Virology
Investigators in the Drexel MIIM graduate program have several areas of research focused around a number of viral pathogens, including HIV, influenza, coronaviruses, HSV, HTLV-1 and HBV. HIV is one of the major focal points; research revolves around viral genetics, elucidating viral reservoirs dynamics, immunopathogenesis and neurologic disease. It also expands to how HIV interacts with and affects other comorbidities like HBV infection and non-AIDS defining cancers, and how drugs of abuse and aging impact these experimental paradigms. In addition, researchers are working on vaccine development, small molecule therapeutics, and “cure” strategies focused on the elimination/inactivation of integrated proviral DNA utilizing CRISPR-Cas9 therapeutic approaches.
To study these questions, MIIM investigators working in collaboration with investigators in the Division of Infectious Diseases & HIV Medicine, and other collaborators across the College of Medicine and University at large, have developed a longitudinal cohort of people living with HIV in the Clinical and Translational Research Support Core (CTRSC) as part of the NIH/NIMH-funded Drexel/Temple Comprehensive NeuroHIV Center (CNHC). The CNHC/CTRSC is involved in the development of facilities and research resources at Temple and Drexel to assist HIV-1 researchers in their experimental endeavors.
In addition, due the overall research prowess around HIV, the faculty within and outside of the department, along with faculty at Temple University School of Medicine, have a large NIH/NIMH-funded T32 training grant for graduate student training in the area of interdisciplinary and translational research training in neuroHIV.
Investigators in the MIIM program also conduct research on HTLV-1, influenza, coronaviruses and herpes simplex viruses. Research on HTLV-1 involves understanding mechanisms underlying associated cancer and neuroinflammation, myeloid/dendritic cell-based immunotherapy and the role of extracellular vesicles in pathogenesis. Influenza research focuses on examining the role of CD8+ T cells in the immune response to viral infection and investigating the innate immune system and its ability to prime the adaptive immune system during infections.
With respect to coronaviruses, research is focused on defining how coronaviruses infect cells, and novel innate immune pathways in the central nervous system during the response to infection. Finally, HSV research guided by departmental faculty focuses on the role of the innate and acquired immune responses involved in resisting HSV-1 infection and novel therapeutic approaches to recurrent disease.