With over 7000 square feet of dedicated research lab space, and a highly accomplished research faculty, ARCOM students will have the opportunity to engage in cutting edge biomedical research. Read more about ongoing medical research at ARCOM and faculty mentors below.
Ross E. Longley, PhD
The overall goal of my research is to discover agents which stimulate and/or regulate the in vitro antitumor activity of immunological cells known as natural killer or “NK” cells (1). A chemically diverse universe of substances known as natural products derived from terrestrial plants and microbes have been shown to possess potent drug-like activities and have been used as chemical scaffolds to develop new agents which have proven to be effective drugs in fighting various types of cancer (2). My lab is involved in the screening of various microbial and plant-derived extracts which will yield compounds whose biological activities stimulate and/or regulate the in vitro, anti-cancer activity of NK cells which results in an enhanced anti-tumor effect. Extracts which are found to be stimulatory to NK cell activity undergo further chemical extraction and purification by our collaborators, and the resulting fractions and pure compounds are further assayed for NK cell activity using flow cytometry. Those compounds which enhance or modulate NK cell activity are further identified as to their chemical structure and their mechanism of action by our collaborators.
- Maelig, G M., and Lanier, L.L. 2016. NK cells and cancer: you can teach innate cells new tricks. Nature Reviews Cancer 16: pp 7-9.
- Longley, R.E. 2012. Discodermolide: Past, present and future. In: Natural products drug discovery. (Frank Koehn, ed.). Springer, New York, NY.
Kenneth Hensley, PhD
My research has long focused on mechanisms of neurodegeneration in diseases including Alzheimer’s disease (HD); amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). I am interested in why neurons deteriorate, rather than how they die. I cannot resurrect a dead neuron but if I can understand why neurons get sick, I might be able to support natural repair pathways in order to improve their health and reduce or even reverse incipient neurodegeneration. Over the past twenty-five years this philosophy has led me to explore many aspects of neuroinflammation, signal transduction and cytoskeletal regulation. One of the most significant outcomes of this effort has been my discovery of a natural brain amino acid metabolite called lanthionine ketimine (LK), which is produced by non-canonical reactions of vitamin B-dependent transulfuration pathway enzymes. My research indicates that both LK and a synthetic, bioavailable LK-ester deriviative (LKE) can suppress neuroinflammation in the damaged brain and support healthy neuron function through the novel mechanism of inhibiting cyclin dependent kinase-5/p25 (Cdk5/p25). My colleagues and I have shown that LKE reduces pathology and restores neural function in rodent models of ALS, AD, stroke, and spinal cord injury. These findings have been published in Biochemistry; Journal of Neuroscience; Journal of Neuropathology and Experimental Neurology; Journal of Neurochemistry; Journal of Neuroscience Research; and other forums. In 2013 I co-founded a company called XoNovo Ltd. to develop LKE as an experimental therapeutic for human brain disease. LKE, now also known as XN-001, is in late-stage preclinical development with an IND application under preparation. The initial clinical target for XN-001 is the pediatric neurodegenerative condition of Batten disease (juvenile neuronal ceroid lipofuscinosis).
I have long enjoyed mentoring undergraduate, graduate and medical students who have contributed to my research projects and co-authored many scientific manuscripts resulting from their work. I plan to continue this practice as I work with local and regional university partners to create new opportunities for undergraduate biomedical research. I feel that ARCOM and its regional academic research partners can synergize in powerful ways to accomplish much greater goals than could be achieved separately. Through such strategic collaborations I hope to help build new models for the conduct of significant biomedical research at Osteopathic medical schools. These goals include discovering and disseminating new knowledge, but primarily emphasize the mission of teaching the practice of evidence-based science to regional students who are likely to matriculate into medical school or otherwise contribute to the 21st century biomedical enterprise.
Swapan Nath, PhD
Health care in the U.S. is facing a crisis in the form of drug-resistant pathogens, and the overuse of antibiotics in both the inpatient and outpatient settings contributes to this problem. “Superbugs” are strains of bacteria that are resistant to several types of antibiotics. The CDC provides the latest data on healthcare-associated infections (HAIs), including Clostridium difficile1 infection and the role of 6 antibiotic-resistant bacteria of “highest concern.” They are: (a) carbapenem-resistant Enterobacteriaceae (CRE), (b) methicillin-resistant Staphylococcus aureus (MRSA)2, (c) extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-Ec), (d) vancomycin-resistant Enterococcus (VRE), (e) multidrug-resistant Gram-negative bacteria (MDR-GNBs: Pseudomonas aeruginosa, and Acinetobacter baumanni). The microbiology labs can help prevent the misuse and overuse of antibiotics. Ideally, doctors would be able to quickly identify the right antibiotic to treat an infection. But labs need days or even weeks to test and identify the bacteria strain. Until the lab results come in, antibiotic treatment is often an educated guess. In my research laboratory, in collaboration with the affiliate hospitals, we will explore what we need to know and how to treat HAIs for a favorable outcome. My laboratory will explore the issues of “antibiotic stewardship” and “niches” of antibiotic-resistant bacteria in the local communities. We will explore and design molecular genetic studies (e.g., “fingerprinting” tools and techniques) to understand the common or unique characteristics of antibiotic-resistant bacteria. Our findings could point the way to contribute to knowledge and understanding of health-care associated infections and control thereof, reducing the additional in-patient days, morbidities, and costs.
- Costas, M., B. Holmes, S.L.W. On, M. Ganner, M.C. Kelly, and S.K. Nath. 1994. Investigation of an outbreak of Clostridium difficile infection in a general hospital by numerical analysis of SDS-PAGE protein patterns. Journal of Clinical Microbiology 32:759-765.
- Nath, S.K., B. Shea, S. Jackson, and C. Rotstein. 1995. Ribotyping of nosocomial methicillin-resistant Staphylococcus aureus isolates from a Canadian hospital. Infection Control Hospital Epidemiology 16:717-724.
Eric Lee, PhD
My research is centered around the role of chronic inflammation in diabetes with two specific areas of interests: 1. The etiology of type II diabetes, and 2. Diabetes complications related to non-healing diabetic ulcers. The etiology based research is focused on the relationship between macrophages and adipocytes in the development of insulin insensitivity with emphasis on the role of IkB-β in crosstalk between inflammatory and insulin cell signaling. The diabetic complications research is focused on developing an understanding the role of IL-6, advanced glycation end-products, and receptors for advanced glycation end-products in the inflammatory phase of delayed diabetic wound healing and diabetic ulcers.
Lance Bridges, PhD
Cell adhesion and migration are integral in a spectrum of biological processes including fertilization, embryonic development, wound healing, cancer metastasis, and immune function. Specifically, the Bridges lab focuses on the role of ADAM (a disintegrin and metalloprotease) proteins in immune cell trafficking. ADAMs are cell surface and soluble glycoproteins uniquely exhibiting both adhesive and proteolytic properties. Catalytically active ADAMs are well-established ectodomain sheddases capable of transforming latent cell-bound substrates to soluble, biologically active derivatives. The sheddase role of ADAMs in processing biologically decisive molecules such as amyloid precursor protein (APP), GPCR activators, cytokines such as TNF-α, and growth factors, has established that dysregulation of ADAM function is detrimental to normal cell function and promotes disease.
The Bridges lab is working on how ADAM-mediate shedding is naturally regulated. The first aspect of this project posits that noncatalytic ADAMs may compete for cellular factors to govern ADAM shedding. Strikingly, of the 21 human ADAMs, nearly half (8/21) inexplicably lack the consensus site required for catalysis. The novel model of regulation tentatively termed “competitive mimicry” may account for the abundance of these “dead” enzymes (see figure below). The second aspect entails metabolic regulation of lymphocyte metalloprotease mediated shedding. Specifically, the role of retinoids, natural and synthetic derivatives of vitamin A, in ADAM regulation is being pursued. The necessity of vitamin A for the proper establishment and maintenance of immunity has long been appreciated, but the precise role of vitamin A in immunity has only begun to be elucidated within the past decade. The Bridges lab has demonstrated that vitamin A oxidative metabolites stimulate immune cell adhesion to select ADAMs through two functionally distinct mechanisms. Currently, investigation into how exposure to metabolites translates into cell adhesion with respect to signal transduction and adhesion receptor expression in context of cutaneous T cell lymphoma are underway.
Julia Moffitt, PhD
Dr. Moffitt’s research program uses a combination of disciplines within the areas of neural control of cardiovascular function and exercise physiology to investigate the interrelationship between the autonomic nervous system, hedonic states and cardiovascular function. The overlying hypothesis is that there is a definite, brain-heart axis and the critical link between hedonic states and cardiovascular function is the autonomic nervous system. Previous studies indicate that disruption in autonomic balance can lead to both altered states of mood or affect and cardiovascular dysfunction, although the mechanisms responsible for these effects are unknown. Continuing studies are focused on disruption of cardiac autonomic balance, the functional physiologic consequences and downstream cellular and molecular mediators responsible. Models for these studies include using cardiovascular deconditioning, aging, acute and chronic electrical stimulation of the vagus nerve, and chronic exercise training. Recent published findings indicate that cardiovascular deconditioning results in withdrawal of cardiac parasympathetic tone and activation of sympathetic tone associated with an increased predisposition to ventricular dysrhythmias. Among the potential cellular mechanisms that mediate these effects are changes in the expression and phosphorylation pattern of the myocardial gap-junction hemi channel Connexin43.