Biomedical Sciences

Research Interests

My research focuses on the biology of aging, with an emphasis on the molecular mechanisms by which natural products influence healthspan and age-related diseases. Using Caenorhabditis elegans as a model, we investigate the neuroprotective effects of oolonghomobisflavans (OFA and OFB), unique compound found in oolong tea in both natural aging and Alzheimer’s disease models, including Aβ and tau pathologies. Through molecular genetics and pharmacogenetic approaches, we explore how these compounds modulate gene-environment interactions and cellular pathways involved in neurodegeneration. Our findings highlight the therapeutic potential of oolong tea-derived compounds in mitigating amyloid and tau toxicity across multiple models, including neuronal cultured cells, C. elegans and Alzheimer’s brain tissue.

As Director of the Appalachian Natural Products Research Program (ANPRP) at Marshall University, I lead efforts to identify bioactive compounds from Appalachian plants with therapeutic potential in aging, cancer, and infectious diseases. My overarching goal is to bridge traditional botanical knowledge with modern molecular science to develop novel interventions that promote healthy aging and improve human health.

Research Interests

I have a varied interest in research with four major research areas. These areas all focus on endothelial cell function and tissue barriers. Though my initial studies focused on transport, my current interest is how health care issues common in Appalachia (Diabetes, hypertension substance abuse) regulate brain endothelial function and what role this plays in psychiatric disorders. My studies have been funded via federal grants at both the PPG and RO1 level. This research has resulted in 43 publications with Pubmed IDs, three other research publications, four book chapters, and one book as an editor, as well as numerous abstracts to scientific conferences.

• The role of other cells (astrocytes, pericytes, neurones, microglia, and various white blood cells) in regulating barrier function has lead to the concept of the “Neurovascular Unit” (NVU).
• What is the role of the BBB /NVU in disease progression? A number of papers have now been published showing changes in BBB structure and function during animal models of disease, or in some cases clinically. What really hasn’t been addressed in many cases is if the BBB changes play an essential role in disease progression, or are a by product of disease progression.

Biography

Dr. Gozal is currently the Dean of the Joan C. Edwards School of Medicine and Vice-President for Health Affairs at Marshall University in West Virginia, a position he assumed in July 2023. He received his M.D. from the Hebrew University of Jerusalem, and MBA degrees from Georgetown University and ESADE, completed his pediatric residency at the Haifa Medical Center in Israel, and then spent 2 years in Cameroon, West Africa, developing rural healthcare networks, for which he received the title of “Knight of the Order of Merit”. He then completed his pediatric pulmonology and sleep medicine training at Children’s Hospital Los Angeles and joined the faculty at the University of Southern California and UCLA. From there he served in leadership roles at various leading universities including University of Chicago, Tulane, University of Louisville and University of Missouri.

He is Past President of the American Thoracic Society and was the third pediatrician to be elected to such high office, was a member of the Board of Directors of the Sleep Research Society 2014-2016. is Senior Deputy Editor-in-Chief for the journal Sleep, and Associate Editor for European Respiratory Journal, Pediatric Pulmonology, and several other journals including AJRCCM. Among his many awards and accolades, he was the recipient of the ATS Amberson Lecture in 2002, the William C. Dement Academic Achievement Award by the American Academy of Sleep Medicine in 2013, and the 2016 Lifetime Achievement Award of the National Sleep Foundation. He has also been bestowed two honorary doctorates from the University of Barcelona and University of Lleida in Spain.  His research work has been continuously supported by grants from the NIH since 1992, has published more than 930 peer-reviewed original articles carrying a H index of 147 and more than 95,000 citations (one of the top 1,000 most cited scientists and one of the top ranked investigators in Medicine in the world), along with nearly 200 book chapters and reviews, edited 7 books including the reference textbook in pediatric sleep medicine, presented more than 1,250 scientific abstracts, and has extensively lectured all over the world.

Research Interests

I have carried out research in a number of areas. However my primary interests have been in extracellular matrix formation and the role of enzymes involved in neurotransmitter synthesis in cardiovascular function, which has resulted in a total of 11 publications. Over the last decade I have concentrated on graduate education, and thus feel that my contribution goes far beyond that of my publication record.

Research Interests

THE NEUROPHARMACOLOGY OF ADDICTION

How do addictive substances alter the brain? How do they create addictive behaviors? All drugs of abuse (cocaine, methamphetamines, nicotine, etc.) alter dopamine release in the human brain. In the case of nicotine, the primary addictive component of tobacco products, dopamine neurons are altered so that more dopamine is released during their highly excitable (phasic) periods of activation. Our lab is studying how specific populations of neurons in the midbrain (dopaminergic, GABAergic, and glutamatergic) are altered by nicotine and how this changes dopamine signaling in the brain. To do this, we use techniques in the fields of electrophysiology, microscopy, pharmacology, and neuroscience to understand how nicotinic acetylcholine receptors (the molecular target of nicotine) play a role in the addiction to nicotine. With the advent of electronic cigarettes, additional flavors that have been banned in traditional cigarettes are now available for smokers of all ages. Therefore, we also study how these flavors may alter the addiction to nicotine.

NEUROPROTECTION

Parkinson’s disease is a form of neurodegeneration that results from the selective degeneration of dopamine neurons in the nigrostriatal pathway (that is, the projection of dopamine neurons from the substantia nigra pars compacta to the dorsal striatum). In recent years it has been made known that smokers exhibit a significantly reduced rate of developing Parkinson’s disease. In addition to studying how nicotine mediates addiction, we are also interested in understanding how nicotine and nicotinic drugs play a role in neuroprotection against Parkinson’s disease.

Henderson Research Website: https://www.hendersonlab.org/

Laboratory Personnel

I am currently recruiting lab members. If you are a grad student interested in a lab rotation, please email me. If you are interested in a postdoc in my lab, please email me with a cover letter and CV containing contact information for at least 3 references.

Research Interest

Abdelnaby Khalyfa, MS, PhD, is an internationally recognized authority in sleep research, specializing in the metabolic and genetic consequences of sleep disorders across murine models and human populations. His groundbreaking work has illuminated the intricate mechanisms underlying obstructive sleep apnea (OSA), with a particular focus on its impacts on pediatric and adult populations.

Dr. Khalyfa’s research has been pivotal in identifying critical associations between OSA and genetic disruptions that drive inflammation, organ dysfunction, and metabolic imbalances. By employing experimental paradigms such as intermittent hypoxia and sleep fragmentation—core physiological features of OSA—his studies have advanced our understanding of the molecular and systemic effects of sleep disturbances.

A trailblazer in the field, Dr. Khalyfa was the first to demonstrate the profound effects of maternal sleep disruption during pregnancy on offspring, revealing how these disturbances predispose future generations to metabolic dysfunction and other health challenges. His innovative work has also extended to extracellular vesicles (exosomes), shedding light on their ability to modulate cell phenotypes in disease states and providing new perspectives on cellular communication in the context of sleep disorders.

Dr. Khalyfa is at the forefront of efforts to identify biological and genetic markers in children and adults with sleep disorders. His lab utilizes cutting-edge techniques such as exosome profiling, gut microbiome analysis, and single-cell sequencing to predict the onset of chronic conditions, including obesity, hypertension, cardiovascular diseases, cancer, and aging. These advancements pave the way for personalized diagnostic tools and therapeutic strategies, with the potential to significantly improve outcomes for individuals affected by sleep disorders.

Research Focus

Dr. Khalyfa’s lab concentrates on three major areas:

1. Sleep Apnea and Aging
2. Sleep Apnea and Metabolic Dysfunction
3. Sleep, Gut Microbiota, and Exosomes in Aging and Metabolic Dysfunction

Research Interests

My long-term research interest is in understanding the etiology and mechanisms underlying Type 2 diabetes and obesity, concomitantly related diseases. Type 2 diabetes is the most common form of human diabetes, accounting for over 90% of cases. Obesity at such epidemic proportions creates serious public health problems. Both diseases, furthermore, are associated with chronic complications and cardiovascular disease, increasing morbidity as well as mortality. 

There is substantial evidence demonstrating that genetic factors are strongly involved in the development of Type 2 diabetes and obesity, and I have focused my attention on the link between gene dysfunction and these diseases. Currently, I seek to understand the molecular basis of an obesity susceptibility gene on mouse chromosome 6, named tabw2, derived from the TALLYHO (TH) mouse model for polygenic Type 2 diabetes and obesity. The Tabw2 gene appears to interact with high fat/ high sucrose diets to make mice overtly obese. In that respect, it is an excellent model for human obesity, which most often results from interactions between genetic susceptibility and an obesity-promoting environment – i.e., diets enriched in calories from fat and sugar. Therefore, understanding the molecular basis for diet-induced obesity in tabw2 mutant mice may uncover new cellular regulatory pathways that can then be exploited in the control of human obesity. I also seek to understand the molecular basis of a diabetes susceptibility gene on mouse chromosome 4, tanidd4, and an obesity susceptibility gene on mouse chromosome 1, tabw3, derived both from the TH mice. The diabetogenic and obesigenic effects of TH alleles at these loci have been confirmed by the congenic mice strategy. Physiological and biochemical characterizations of diabetes and obesity mediated by these loci are also ongoing using the congenic mouse strains. My continued research will include gene discovery, genetic resource development, and biochemical and physiological studies associated with Type 2 diabetes and obesity.

Laboratory Personnel

Jacaline K. Parkman, B.S. – Research M.S. student