In the Wainger Lab, we strive to foster Diversity, Equity, Inclusion and Belonging and support the MGH statement: “Diversity is the richness of human differences. Inclusion is when everyone feels connected, valued and engaged. At Massachusetts General Hospital, we believe that because of diversity we excel; through inclusion we respect; focused on equity we serve, heal, educate and innovate.
Projects
ALS RESEARCH
Amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig’s disease, is a devastating neurological disease of the motor nervous system. Within a few short years, its victims fall from good health—often in the prime of life—and ultimately perish due to progressive motor neuron deterioration. ALS is surprisingly common: people have a lifetime risk of about 1 in 400. Our goal is to identify and test novel therapeutics for rapid translation of ALS treatments.
Our team is part of the MGH Healey Center for ALS Research. We previously identified abnormalities in the electrical activity of motor neurons derived from ALS patients using stem cell technology. The research culminated in identifying the importance of Kv7 channels as drivers of hyperexcitability in ALS and successfully demonstrating that Kv7 agonist retigabine (also called ezogabine) reduces this pathological hyperexcitability in a phase 2, 12-site clinical trial of ALS subjects. In the lab, we use iPSC-derived motor neurons and organoids to model the molecular mechanisms of ALS. We are evaluating candidate therapeutics and performing screens to identify new and more powerful potential targets and treatments.
CHRONIC PAIN PRECLINICAL RESEARCH
Chronic pain causes profound impairments in quality of life, mood and functioning. It affects over one quarter of adult Americans and is one of the most common reasons for physician visits, lost productivity and disability. Ongoing work in our group has led to stem cell based models to better understand pain drivers in human neurons. We have developed an assay platform that provides single-cell excitability readouts on individual pain-sensing neurons, as well as the capacity to classify the subtype of each neuron involved. Using pain-sensing neurons from both human stem cells and mice, we have used this assay to screen compound libraries and validate novel hits. Given the recent successes of gene-therapy based strategies in medicine, we have made novel advances to selectively modify the excitability of pain neurons, without the side effects that result from a less targeted strategy. This strategy is being developed with a goal of clinical translation.
X-LINKED DYSTONIA PARKINSONISM
X-Linked dystonia Parkinsonisms is a rare neurodegenerative disease characterized by progressive dystonia and Parkinsonian symptoms. Our team, within the Center for Collaborative Center for X-Linked Dystonia Parkinsonism, focuses on stem cell modeling of disease components.
CLINICAL RESEARCH
Our group is performing two studies within the NIH HEAL Initiative using neurophysiological techniques to help identify mechanism-based biomarkers in chronic pain. One project is investigating mechanisms of spinal cord stimulator reduction in pain and will include measurements of nerve excitability using threshold tracking and microneurography as well as PET imaging of neuroinflammation in the brain. This study is led by our group, Dr. Roy Freeman, and Dr. Marco Loggia, and is a collaboration including researchers and clinicians at Massachusetts General Hospital, Beth Israel Deaconess Medical Center, and Brigham and Women’s Hospital. A second project, led by Dr. Seward Rutkove and our group, is investigating physiological and ultrasound biomarkers of myofascial pain. The study is a collaboration between Beth Israel Deaconess Medical Center and Massachusetts General Hospital.
The combination of specialized clinical and research training places the group in a prime position to investigate disease-related research questions and find practical and promising ways to directly advance the application of basic science research to clinical medicine.
