At Jefferson, Dr. Jay Nair is leading neurorehabilitation research that aims to optimize and improve the precision of neurotherapeutic approaches for individuals living with neurological injuries or diseases. His laboratory is currently working on developing novel neuro-therapeutic approaches that combines the use of acute intermittent hypercapnic-hypoxia (a mild form of therapeutic neurochemical challenge) with non-invasive transcutaneous spinal direct current stimulation to prime the nervous system for activity based physical rehabilitation. Additionally, he is also working on developing natural history of disease in neurodegenerative disorders such as Amyotrophic lateral sclerosis (ALS). Dr. Nair employs functional movement testing and electrophysiological recording to study humans with central nervous system injuries and diseases. His laboratory also employees molecular techniques to analyze saliva and blood bio specimens for genetic and inflammatory markers that differentiate responders from non-responders to physical rehabilitation interventions. 

Dr. Nair is a Physical Therapist with over two decades of experience as a clinician, educator and researcher.  He received his PhD in Rehabilitation Science from University of Florida in 2016. Prior to joining as Assistant Professor in the department of Physical Therapy at Thomas Jefferson University, he completed two post-doctoral training at University of Florida which include training in Molecular Genetics (2016-2019) and Respiratory Neurorehabilitation research (2020-2022). 

Combinatorial Treatment with Intermittent Hypercapnic-Hypoxia and Transcutaneous Spinal Stimulation for Movement Recovery in Chronic Spinal Cord Injury

Spinal cord injury (SCI) disrupts neural connections between the brain and neurons in the spinal cord resulting in paralysis or weakness in the affected muscles. Among SCI, injury to the neck (cervical) region is the most severe as it is associated with use of mechanical ventilators to breath, loss of functional independence, increased burden of care, along with higher rates of infection, re-hospitalization and death after SCI. This is primarily due to loss of movement control in important breathing muscles (C3-C5) and muscles of upper extremity (C4-T1). Although functional exercise based physical rehabilitation is effective in the acute stages of SCI, its effectiveness in inducing spinal plasticity plateaus as the injury becomes chronic. Thus, a novel therapeutic intervention that facilitate spinal neuroplasticity in the chronic stage of SCI is critically needed. Acute intermittent hypercapnic-hypoxia (AIHH) – a noval, non-invasive treatment that involves breathing short episodes of low oxygen combined with slightly elevated carbon-dioxide, to promote restoration of breathing and limb functions by enhancing neural plasticity in the spared neural pathways. Similarly, noninvasive transcutaneous spinal cord stimulation (tSCS)– is a novel strategy to promote spinal neuroplasticity by lowering the firing threshold of spinal cord neurons. In collaboration with Jefferson Center for Neurorestoration, Dr Nair is testing whether combinatorial treatment with AIHH and tSCS paired functional training will enhance the rate of recovery of breathing and upper extremity function in individuals living with chronic SCI. 

Early functional and MR based biomarkers for natural history of ALS disease progression

Amyotrophic lateral sclerosis (ALS) is the most common (incidence: 6/100k annually) adult onset progressive neurodegenerative disease that leads to muscle weakness, paralysis and death due to decreased capacity to breath. The loss of muscle function occurs due to ALS associated progressive degenerative changes in the brainstem and spinal cord motor neurons that control these muscles. Although ~15% of ALS disease has a familial onset, no medical guidelines exist for early diagnosis and timely intervention for siblings at risk with identical genetic risk factors such as presence of C9orf72 and SOD1 mutant genes. Currently, most of these individuals wait without medical intervention until ~1 year after the onset of their first clinical symptoms, at which point the therapeutic window to effectively intervene with novel gene therapy approaches is lost. Dr. Nair is working in collaboration with Jefferson Weinberg ALS Center, and Jefferson Magnetic Resonance Imaging Center (JMRIC) to develop a natural history of disease progression using MRI for asymptomatic phase of ALS. In this research project the MRI based changes in the spinal cord and muscles is correlated with changes in the muscle function to detect earliest signs of ALS disease progression in asymptomatic genetically linked siblings of patients with familial ALS. These novel early biomarkers of ALS disease has the potential to shift the current clinical practice paradigm from a palliative and supportive care of ALS to a proactive medical care by effectively timing disease ameliorating therapies to rescue sick motor neurons in risk siblings of patients with familial onset of ALS disease.    

Genetic Biomarkers of Intermittent Hypoxia-Induced Respiratory Motor Plasticity in Chronic Spinal Cord Injury

Cervical spinal cord injury is associated with damage to the respiratory neural pathways resulting in decreased capacity to breath and increased risk of life threatening respiratory illness. In this Department of Defense funded clinical trial the goal is to optimize acute intermittent hypoxia (AIH), a non-invasive treatment that involves short bouts (1 min) of breathing low oxygen by 1) combining hypoxia with hypercapnia (5% inspired CO2) during each episode (AIHH) to augment respiratory motor plasticity; 2) combining AIHH with an established form of task specific training (respiratory strength training); and, 3) identify genetic biomarkers distinguishing those most/least likely to benefit from AIH-based treatments. Dr. Nair is serving as a collaborator on this grant based at University of Florida.