Brian Wainger, MD, PhD

Wainger Laboratory

The Wainger Lab at Massachusetts General Hospital focuses on how abnormalities of motor and sensory neuron physiology contribute to diseases such as ALS and chronic pain.

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.

Group Members

Principal Investigator

Brian J. Wainger, MD, PhD
Assistant Professor of Neurology and Anesthesiology, Critical Care and Pain Medicine

Dr. Wainger is Assistant Professor in Anesthesiology and Neurology at Harvard Medical School and an attending physician at Massachusetts General Hospital.

He studied molecular biology as an undergraduate at Princeton University, and ion channel physiology in the MD/PhD program at Columbia University.

He then completed medical residency in the Partners Neurology Program, followed by a clinical fellowship in Pain Medicine at Mass General, research fellowship with Clifford Woolf at Boston Children’s Hospital and clinical investigator training through the Harvard Master’s Program in Clinical and Translational Investigation.

Dr. Wainger's clinical expertise spans the intersection of neurology and pain medicine.

Laboratory Staff

Harukho (Harry) Banno, Clinical Fellow
Anna-Claire Devlin, Postdoctoral Fellow
Julian Gal, Research Assistant
Daniel Moakley, Research Assistant
Joao Pereira, Postdoctoral Fellow
Yechiam Sapir, Postdoctoral Fellow

LocationBuilding 114, Charlestown Navy Yard
114 16th St., Room 2007
Charlestown, MA 02129

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.

Publications

  1. Wainger BJ, Buttermore ED, Oliveira JT, Mellin C, Lee S, Afshar Saber W, Wang A, Ichida JK, Chiu IM, Barrett L, Huebner EA, Bilgin C, Tsujimoto N, Brenneis C, Rubin LL, Eggan K, Woolf CJ. Modeling pain in vitro using noceptors reprogrammed from fibroblasts. Nature Neuroscience, 2014, in press.
  2. Wainger BJ, Kiskinis EK, Mellin C, Wiskow O, Han S, Sandoe J, Perez NP, Williams AL, Lee S, Boulting G, Berry JD, Brown RH, Cudkowicz ME, Bean BP, Eggan K, Woolf CJ. Intrinsic membrane hyperexcitability of ALS patient-derived motor neurons. Cell Reports  2014;7:1-11
  3. Kiskinis E, Sandoe J, Williams LA, Boulting GL, Moccia R, Wainger BJ, Han S, Peng T, Thams S, Mikkilineni S, Mellin C, Merkle FT, Davis-Dusenbery BN, Ziller M, Oakley D, Ichida J, Dicostanza, S, Atwater N, Maeder ML, Goodwin MJ, Nemesh J, Handsaker RE, Paull D, Noggle S, McCarroll SA, Joung JK, Woolf CJ, Brown RH, Eggan K. Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1. Cell Stem Cell  2014;14:81-95
  4. Chiu IM, Heesters BA, Ghasemlou N, Von Hehn CA, Zhao F, Tran J, Wainger BJ, Strominger A, Muralidharan S, Horswill AR, Wardenburg JB, Hwang SW, Carroll MC, Woolf CJ. Bacteria activate sensory neurons that modulate pain and inflammation. Nature 2013;501:52-7.
  5. Yang YM, Gupta SK, Kim KJ, Powers BE, Cerqueira A, Wainger BJ, Ngo HD, Rosowski KA, Schein PA, Ackeifi CA, Arvanites AC, Davidow LS, Woolf CJ, Rubin LL. A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS. Cell Stem Cell 2013;6:713-26
  6. Hanada T, Weitzer S, Mair B, Bernreuther C, Wainger BJ, Ichida J, Hanada R, Orthofer M, Cronin SJ, Komnenovic K, Minis A, Sato F, Mimata H, Yoshimura A, Tamir I, Rainer J, Kofler R, Yaron A, Eggan KC, Woolf CJ, Glatzel M, Herbst R, Martinez J, Penninger JM. CLP1 links tRNA metabolism to progressive motor neuron loss. Nature  2013;495:474-80.
  7. Son EY, Ichida JK, Wainger BJ, Toma JS, Rafuse VF, Woolf CJ, Eggan K. Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell  2011;9:205-18.
  8. Wainger BJ, DeGennaro M, Santoro B, Siegelbaum SA, Tibbs GR. Molecular mechanism of cAMP modulation of HCN pacemaker channels. Nature  2001;411:805-10.

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