Martin Childers, DO, PhD
Disclosures: I/we have no financial relationships to report.
OMB No. 0925-0046, Biographical Sketch Format Page

OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)

BIOGRAPHICAL SKETCH

Provide the following information for the Senior/key personnel and other significant contributors.
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NAME: Childers, Martin Kent

eRA COMMONS USER NAME (credential, e.g., agency login): CHILDERSMK

POSITION TITLE: Professor

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

INSTITUTION AND LOCATION

DEGREE

(if applicable)

 

Completion Date

MM/YYYY

 

FIELD OF STUDY

 

 

Seattle Pacific University

 

BA

 

05/80

 

Music Performance

Western University

DO

05/90

Medicine

University of Missouri

PhD

05/02

Physiology and Pharmacology

 

 

 

 

 

 

 

 

 

  1. Personal Statement

The goal of our primary research is to address the major hurdles in the field of gene therapy for patients with inherited diseases of skeletal muscle. We exploit a novel large animal model of a congenital myopathy, termed, X-linked myotubular myopathy (XLMTM). Dogs with a naturally occurring mutation develop XLMTM. Studies in XLMTM dogs facilitate rapid translation to patients suffering from cardio-respiratory dysfunction and certain death. As a key collaborator in this investigation, I command a broad background in medical physiology, with specific training and expertise in key research areas for this application.  About 20 years ago as a medical resident at the University of Missouri, I trained under the mentorship of Joe Kornegay, the world’s leading authority in the canine model of Duchenne muscular dystrophy.  A subsequent KO8 award provided me the opportunity to study dystrophic dog skeletal muscle mechanics at the whole muscle and single fiber levels. As a faculty member, I conducted pivotal multicenter drug trials in patients, and am currently lead investigator in a preclinical gene therapy trial for XLMTM, a study that will lead to generating data needed for application for an investigative new drug (IND) to the FDA. The current R01 proposal exploits the dog model builds and builds logically upon our collective experience in gene therapy, genetics, molecular biology and physiology. Our group is part of the NIH Wellstone Muscular Dystrophy Center at UW.  Together, our team provides expertise in virology, gene therapy, pathology, physiology, and immunology – all working together to tackle a challenging and exciting approach to address key challenges in the field of gene therapy.

 

 

  1. Positions and Honors.

 

Positions and Employment

1990-1991                            Intern, Department of Internal Medicine; Sun Coast Hospital, Largo, FL

1991-1994                            Emergency Physician, Still Regional Medical Center, Jefferson City, MO                                                                     

1991-1994              Resident Physician, Dept. of Physical Medicine & Rehabilitation (PM&R), University of Missouri-Columbia                           

1994-2000                            Assistant Professor, Dept. of PM&R, University of Missouri-Columbia

2000-2006                            Associate Professor, Dept. of PM&R, University of Missouri-Columbia

2006-2009                              Associate Professor, Dept. of Neurology, Wake Forest University Health Sciences

2009-2012               Professor (with tenure), Dept. of Neurology, and Institute for Regenerative Medicine, Wake Forest University Health Sciences

2012-present              Professor, Department of Rehabilitation Medicine, University of Washington School of Medicine             

 

Editorial Boards

Board Member:

2011 – Present                            TheScientificWorldJOURNAL

2010 – Present                            Frontiers in Integrative Pharmacology

2008 – Present                            PM & R Journal

2004 – 2009                                           American Journal of Physical Medicine & Rehabilitation

                           

                                                                     

Other editorial work

Ad Hoc Reviewer:

2016 _ Present           Science Translational Medicine

2016 _ Present           Molecular Medicine

2010 – Present              PLOS One

2011 – Present              Journal of Urology

2010 – Present              Human Molecular Genetics

2010 – Present              Recent Patents on Regenerative Medicine

2009 – Present              Neuromuscular Disorders

2008 – Present              Journal of Tissue Engineering & Regenerative Medicine

2004 – Present              Journal of Applied Physiology

2000 – 2004                            Brain Injury

2002 – Present              Pain

2001 – Present              Muscle and Nerve

1999 – Present              Archives of Physical Medicine and Rehabilitation

 

Study sections and other grant review committees

 

2016 -2021              Scientific Advisory Committee, standing member, Muscular Dystrophy Association

2015              PAR Panel: Animal Models and Stem Cell-based Therapies for Regenerative Medicine  ZRG1 CB-J (55) R

2012 - 2015              Medical Advisory Committee, Muscular Dystrophy Association

2011              Distinguished Editor, Musculoskeletal, Oral and Skin Sciences (MOSS) study section special emphasis panel (ZRG1 MOSS-C90)

2006 – 2011              Intramural Research Support Committee, Wake Forest University School of Medicine

2004 – 2009              NIH (NIAMS, NINDS) Skeletal muscle exercise physiology (SMEP) study section (ad hoc)

2002 – 2006              US Army, American Institute of Biological Sciences (annual review of DMD programs)

2002 – 2006              Advisory Board for the Spinal Cord Injuries or Acquired Disease Processes Research Program, Office of the President of the University of Missouri

2001 – 2006              Roger S. Williams Fund Board of Trustees, School of Health Professions, University of Missouri

 

 

C. Contributions to Science

1. Physiology of dystrophin deficiency in skeletal muscle. My early publications address issues related to physiological and phenotypic characteristics of muscle disease in a canine model of muscular dystrophy. These canine studies demonstrate our experience conduction muscle physiology studies in dogs.

 

  1. Childers MK*, Okamura CS, Bogan DJ, Bogan JR, Petroski GF, McDonald K, Kornegay JN. Eccentric contraction injury in dystrophic canine muscle. Arch Phys Med Rehabil 2002;83(11):1572-8.
  2. Childers MK*, Staley JT, Kornegay JN, McDonald KS. Skinned single fibers from normal and dystrophin-deficient dogs incur comparable stretch-induced force deficits. Muscle Nerve 2005;25;31(6):768-771.
  3. Childers MK*, Staley JT, Kornegay JN, McDonald KS. Skinned single fibers from normal and dystrophin-deficient dogs incur comparable stretch-induced force deficits. Muscle Nerve 2005;25;31(6):768-771.
  4. Tegeler C, Grange RW, Bogan DJ, Markert CD,  Case D, Kornegay JN, Childers MK*. Eccentric contractions induce rapid isometric torque drop in dystrophin-deficient dogs. Muscle Nerve 2010 Jul;42(1):130-2.PMID: 20544944.

 

2. Cellular reprogramming of urine cells from muscular dystrophy patients. My lab was first to extract and reprogram urine stem cells from DMD to pluripotent stem cells. These unique cell lines have been used by our group and others to generate heart cells carrying dystrophin mutations

  1. Pioner JM, Racca AW, Klaiman JM, Yang KC, Guan X, Pabon L, Muskheli V, Zaunbrecher R, Macadangdang J, Jeong MY, Mack DL, Childers MK, Kim DH, Tesi C, Poggesi C, Murry CE, Regnier M. Isolation and Mechanical Measurements of Myofibrils from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Stem Cell Reports. 2016 Jun 14;6(6):885-96. PMID: 27161364.

b.   Afzal MZ, Reiter M, Gastonguay C, McGivern JV, Guan X, Ge ZD, Mack DL, Childers MK, Ebert AD, Strande JL. Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy. J Cardiovasc Pharmacol Ther. 2016 Nov;21(6):549-562. PubMed PMID: 26940570; PubMed Central PMCID: PMC5010518.

c.  Macadangdang J, Guan X, Smith AS, Lucero R, Czerniecki S, Childers MK, Mack DL, Kim DH. Nanopatterned Human iPSC-based Model of a Dystrophin-Null Cardiomyopathic Phenotype. Cell Mol Bioeng. 2015 Sep;8(3):320-332. PubMed PMID: 26366230; PubMed Central PMCID: PMC4564135.

d. Guan X, Mack DL, Moreno CM, Strande JL, Mathieu J, Shi Y, Markert CD, Wang Z, Liu G, Lawlor MW, Moorefield EC, Jones TN, Fugate JA, Furth ME, Murry CE, Ruohola-Baker H, Zhang Y, Santana LF, Childers MK. Dystrophin-deficient cardiomyocytes derived from human urine: new biologic reagents for drug discovery. Stem Cell Res. 2014 Mar;12(2):467-80. doi: 10.1016/j.scr.2013.12.004. PubMed PMID: 24434629; PubMed Central PMCID: PMC3966181.

 

3. Physiology of myotubularin deficiency in dogs. My lab was first to establish a canine model of a rare neuromuscular disease, myotubular myopathy. These experiments set the stage for a large preclinical gene therapy trial supporting future clinical trials and demonstrate our experience working with this unique animal model.

 

a. Beggs AH, Böhm J, Snead E, Kozlowski M, Maurer M, Minor K, Childers MK, Taylor SM, Hitte C, Mickelson JR, Guo LT, Mizisin AP, Buj-Bello A, Tiret L, Laporte J, Shelton GD. MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14697-702. PMID: 20682747.             

b. Grange RW, Doering J, Mitchell E, Holder MN, Guan X, Goddard M, Tegeler C, Beggs AH, Childers MK*. Muscle function in a canine model of X-linked myotubular myopathy. Muscle Nerve. 2012 Oct;46(4):588-91. doi: 10.1002/mus.23463. PubMed PMID: 22987702; PubMed Central PMCID: PMC3448125.

c. Goddard MA, Mack DL, Czerniecki SM, Kelly VE, Snyder JM, Grange RW, Lawlor MW, Smith BK, Beggs AH, Childers MK*. Muscle pathology, limb strength, walking gait, respiratory function and neurological impairment establish disease progression in the p.N155K canine model of X-linked myotubular myopathy. Ann Transl Med. 2015 Oct;3(18):262.

e. Childers MK*, Joubert R, Poulard K, Moal C, Grange RW, Doering JA, Lawlor MW, Rider BE, Jamet T, Danièle N, Martin S, Rivière C, Soker T, Hammer C, Van Wittenberghe L, Lockard M, Guan X, Goddard M, Mitchell E, Barber J, Williams JK, Mack DL, Furth ME, Vignaud A, Masurier C, Mavilio F, Moullier P, Beggs AH,Buj-Bello A. Gene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy. Sci Transl Med. 2014 Jan 22;6(220):220ra10.doi: 10.1126/scitranslmed.3007523. PubMed PMID: 24452262.

 

Complete List of Published Work in MyBibliographyhttp://www.ncbi.nlm.nih.gov/myncbi/browse/collection/40458014/?sort=date&direction=descending

 

D. Research Support.

 


 

Ongoing Research Support

 

1R01HL115001-01A1                                                                                                  Childers (PI)                                                                                                                      05/01/13 – 04/30/18

NIH/NHLBI. Gene therapy in canine myotubular myopathy for clinical translation

The goal of this preclinical study in XLMTM dogs is to determine efficacy of various AAV constructs carrying MTM1.

 

Industry Support                                                                                                                Childers (PI)                                                                                                                                    05/01/13 – 04/30/17

Audentes Therapeutics. Dose-response study of recombinant AAV in canine myotubular myopathy

The goal of this preclinical study in XLMTM dogs is to determine the minimal effective dose of AAV8 carrying MTM1.

 

5U54AR065139-02                                                                                                  Chamberlain (PI)                                                                                                                05/01/14 – 04/31/19

SEN PAUL D. WELLSTONE MUSCULAR DYSTROPHY COOPERATIVE RESEARCH CENTER: SEATTLE

The goal of Project 1 focuses on adapting methods for AAV-mediated gene transfer to large animal models for DMD by focusing on expression cassette design, AAV serotypes, physical delivery methods and scale-up.                                Role: PI for Project 1.

 

Completed Research Support

 

R01NS042874                                                                                                                     Stedman HH (PI)                                                                                                     12/01/01 -03/31/14   

NIH/NINDS    

Systemic Molecular Therapy for Muscular Dystrophy

This project test several hypotheses regarding systemic effects of AAV-mediated gene therapy in dogs with muscular dystrophy.

Role: Co-I

 

1R21AR064503-01A1                                                                                                  Childers (PI)                                                                                                                              09/12/12 – 08/31/14

NIH/NIAMS

Establishing endpoints in canine myotubular myopathy for clinical translation

The goal is to study the natural history of disease progression in the dog model of XLMTM

Role: PI

 

 

MDA201127                                                                                                                              Childers (PI)                                                                                                                              08/1/11 – 07/31/14

MDA Research Grant: Dystrophin-deficient Cardiomyocytes for High Throughput Screening

The goal is to produce iPS cell lines from patients with Duchenne muscular dystrophy (DMD), isolate cardiac lineage progenitors derived from these stem cells, and screen DMD cardiomyocytes to discover new drugs.

Role: PI

 

 

MDA Academic Translational Grant                               Childers (PI)                                                                                                                              05/01/11 – 04/30/14

Gene therapy in canine myotubular myopathy

The goal is to test efficacy and safety of AAV-MTM1 in a canine model of X-linked myotubular myopathy

Role: PI

 

Association Francaise contre les Myopathies (AFM)

Research Grant                                                                                                                  Childers (PI)                                                                                                                               05/01/11 – 04/30/14

Gene therapy in canine myotubular myopathy (Matching funds to MDA Academic Translational Grant)

The goal is to test efficacy and safety of AAV-MTM1 in a canine model of X-linked myotubular myopathy

Role: PI