Wainger Laboratory: Brian Wainger, MD, PhD

Overview

The aim of the Wainger Laboratory is to ask clinically relevant research questions that could lead to rapid translation and innovation for treating diseases of the motor and sensory nervous systems.

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. 

Prior investigation led by Brian Wainger, MD, PhD, (Wainger et al., Cell Stem Cell, 2014) has identified abnormalities in the electrical activity of motor neurons derived from ALS patients using stem cell technology. The research culminated in the discovery of the FDA-approved drug retigabine (ezogabine) as a candidate therapeutic, and this drug will now be investigated further in a clinical trial of ALS subjects.

Chronic Pain Research

Chronic pain does not have the same lethal impact as ALS; however, any sufferer of chronic pain can testify to the profound impairments in quality of life, mood and functioning that plague pain patients. Chronic pain affects over one quarter of adult Americans and is one of the most common reasons for physician visits, lost productivity and disability.

Ongoing work by Dr. Wainger has yielded a technique for deriving pain-sensing neurons from patient skin samples (Wainger et al., Nature Neuroscience, 2014, in press). This novel method may offer a way to investigate causes of pain in human patients, thus potentially overcoming the limits of animal models, which have resulted in only limited success in identifying effective treatments for human pain. The goal is to use the human pain-sensing neurons to identify and evaluate novel treatments for pain in patients.

The combination of specialized clinical and research training places Dr. Wainger 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.

Research Projects

The research laboratory of Brian Wainger, MD, PhD, is focused on understanding how the physiological properties of motor and sensory neurons may yield insight into relevant diseases such as amyotrophic lateral sclerosis (ALS) and painful neuropathy. We believe that such investigation is promising because abnormal neuronal excitability is a key clinical feature in both ALS and chronic pain.

Phenomena such as fasciculations (small, involuntary muscle contractions) and abnormal cortical excitability assessed by transcranial magnetic stimulation in ALS, as well as features of neuropathic pain, such as spontaneous pain and pain in response to light touch, all reflect abnormal neuronal activity.

We employ stem cell-based modeling, primary human tissue and mouse models. We use patch-clamp, extracellular multi-electrode array recording, calcium imaging as well as molecular and genetic tools to obtain insight into disease mechanisms that we can then use to translate into potential new clinical therapies.

As part of the MassGeneral Institute for Neurodegenerative Disease, we are well-suited to develop hypotheses using stem cell-derived and mouse neurons and then test the hypotheses using human neurons from post-mortem samples. 

Research Positions

We are looking for creative, talented, successful and enthusiastic graduate students and post-doctoral scientists to join our group. To learn more about open positions in the Wainger Laboratory, please contact us by email.

Selected Publications

Pereira JD, DuBreuil DM, Devlin AC, Held A, Sapir Y, Berezovski E, Hawrot J, Dorfman K, Chander V, Wainger BJ. Human sensorimotor organoids derived from healthy and amyotrophic lateral sclerosis stem cells form neuromuscular junctions. Nat Commun. 2021 Aug 6;12(1):4744. doi: 10.1038/s41467-021-24776-4. PMID: 34362895

DuBreuil DM, Chiang BM, Zhu K, Lai X, Flynn P, Sapir Y, Wainger BJ. A high-content platform for physiological profiling and unbiased classification of individual neurons. Cell Rep Methods. 2021 May 24;1(1):100004. doi: 10.1016/j.crmeth.2021.100004. Epub 2021 Apr 2. PMID: 34318289

Weiss MD, Macklin EA, McIlduff CE, Vucic S, Wainger BJ, Kiernan MC, Goutman SA, Goyal NA, Rutkove SB, Ladha SS, Chen IA, Harms MB, Brannagan TH, Lacomis D, Zivkovic S, Ma M, Wang LH, Simmons Z, Rivner MH, Shefner JM, Cudkowicz ME, Atassi N; Mexiletine-2 ALS Study Group. Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial. Muscle Nerve. 2021 Mar;63(3):371-383. Epub 2020 Dec 31.