Stony Brook University

Grigori Enikolopov, PhD, Professor

The Enikolopov laboratory’s main focus is on stem cells in the adult organism and on signals controlling their maintenance, division and fate. Most of the effort is directed at stem cells of the adult brain and on the signaling landscape of the neural stem cell niche. They also are interested in stem cells in non-neural tissues, with a particular focus on those tissues and organs that are involved in complex physiological circuits and major physiological and behavioral responses of the organism. They also study how diffusible signaling molecules affect stem cell maintenance, differentiation, and interactions with the local environment. Furthermore, they work to generate new genetic tools that would allow tracking multiple signaling events in a cell or a tissue. Besides the main goal of elucidating the molecular logic of the stem cell control, Dr. Enikolopov considers these studies as an entry point for designing therapeutic interventions to ameliorate the deleterious effects of aging or disease. Their work is supported by the National Institute of Aging, the National Institute of Neurological Disorders and Stroke, the National Heart, Lung and Blood Institute, and by the New York Stem Cell Foundation (NYSTEM).

Martin Kaczocha, PhD, Assistant Professor

Acute and chronic pain is treated with analgesics that are oftentimes partially effective, induce significant side effects, and carry risks of addiction. The Kaczocha laboratory’s primary research interests are in the area of bioactive lipids and their roles in inflammation and pain, with the long-term goals of developing novel therapeutics for pain. Our work demonstrates that inhibition of fatty acid binding proteins, intracellular carriers for bioactive lipids, produces analgesic effects in rodent models of pain. In collaboration with the Institute of Chemical Biology and Drug Discovery, the laboratory is currently developing fatty acid binding protein inhibitors that may serve as novel analgesic and anti-inflammatory agents. We have also embarked in new directions that examine the contributions of endocannabinoid/eicosanoid crosstalk towards postoperative pain and whether inhibitors of this pathway may serve as novel analgesics. Research in the laboratory is supported by NIH grants DA035949 and DA035923.

Michelino Puopolo, PhD, Assistant Professor

Chronic pain is a debilitating condition that affects at least 15% of the US population and accounts for annual economic losses, including productivity, of over $600 billion. Despite decades of research identifying potential targets, few pharmacotherapies have proven effective, and most offer only partial symptomatic relief while introducing significant side effects and risks of addiction. The Puopolo laboratory is exploring new therapies for pain relief that specifically target the pain transmission pathways themselves. The dorsal horn of the spinal cord represent the first relay station where pain signals from nociceptors are modulated and integrated before moving to supraspinal centers. The synaptic transmission from nociceptors to the dorsal horn of the spinal cord can be regulated by neurotransmitters acting through a variety of G-protein-coupled-receptors (GPCRs). Some of these neuromodulators, such as opiates, are released from neurons intrinsic to the spinal cord, while others, such as norepinephrine, serotonin, and dopamine are released from descending fibers. Hypothalamic A11 dopamine neurons project to all levels of the spinal cord and provide the main source of dopamine. The focus of the laboratory is to explore the descending dopaminergic system as a potential locus for pain modulation. They use patch clamp electrophysiology in isolated DRG neurons and spinal cord slices to study the effects of dopamine on the intrinsic excitability and synaptic transmission from nociceptors to lamina I projection neurons. Complementary approaches, in collaboration with Dr. Kaczocha, include dopamine receptor biochemistry, immunohistochemistry, and behavioral measurements in vivo. Gaining insight into the cellular and molecular mechanisms of how dopamine receptors regulate the intrinsic excitability and synaptic transmission from nociceptors will be useful to identify new pharmacological targets and for developing more effective therapeutics to reduce or ameliorate chronic pain.

Lixin Liu, MD PhD, Associate Professor

Most myocardial infarctions occur in older persons, and the associated morbidity and mortality are greater with advancing age. Aging is also associated with impaired cardiac preconditioning and cardiprotection. To better understand this age-associated difference, Dr. Liu‘s main focus is on understanding the mechanisms underlying failure of various pharmacotherapies to protect the old myocardium. The laboratory uses ischemia reperfusion injury in an aging rat model, as well as ventricular myocytes isolated from senescent animals to test various strategies aimed at restoring cardioprotection. Both her basic research and her patient care centers on cardiac protection, particularly for aged patients undergoing surgery. As an anesthesiologist, she sees first-hand the complexities associated with having older and sicker patients presenting for surgery. As a basic scientist, she sees how the aging process and oxidative stress influences gene expression patterns, signal transduction pathways and mitochondrial function. Her long term goal is to understand the mechanisms underlying the loss of pharmacologic preconditioning in the aged myocardium, to develop therapeutic strategies that can restore the cardioprotective effects of anesthesia preconditioning (APC) and other agents in the aged heart, and to translate these findings into clinical approaches that could benefit the elderly population at risk for adverse cardiac events during the perioperative period.

Joshua Dubnau, PhD, Professor

A major focus of the research in Dr Dubnau's lab is to investigate the mechanism of age-related neurodegenerative dementias. These include amyotrophic lateral sclerosis (ALS) and Frontotemporal lobar degeneration (FTLD) and, perhaps, Alzheimer's. The Dubnau group has proposed the novel hypothesis that age-related neurodegenerative disorders involve activation of retrotransposons. Retrotransposons are viral-like genetic entities that make up approximately 40% of the human genome. Recent publications from Dr Dubnau and his team support the idea that the effects of aging interact with the impact of environmental stress and genetic predisposition to disrupt the normal cellular systems that normally stifle retrotransposon activation. This may result in a storm of awakened retrotransposons, with neurotoxic effects. The Dubnau lab is investigating this hypothesis using a multidisciplinary approach that includes in vivo genetic experiments in animal models, analysis of post mortem human tissue, and cell culture assays. Dr Dubnau and his team are currently supported by research grants from NINDS, NIDCD, NIA, Ride For Life, and DART Neuroscience LLC.