Brantly Lab


 

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Mark Brantly, MD
Professor of Medicine
Vice Chair of Research, Department of Medicine
Alpha-1 Foundation Research Professor
mark.brantly@medicine.ufl.edu

Personal Statement

I am senior investigator specializing in rare lung disease translational research with a focus on alpha-1-antitrypsin deficiency, gene therapy, pulmonary fibrosis and alveolar macrophage function. I have mentored a number faculty in bench to bedside research at the NIH Clinical Center and the University of Florida. I am a former K24 grantee, a mentor on 2 T32 programs and the UF MD/PhD program. My role on applicant’s grant is to provide molecular biology support, access to lung tissue and guidance on the transition to patient-oriented research.

 

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Positions and Honors

 

Professional Experience:

1986-1989      Parker B. Francis Fellow, Pulmonary Branch, NHLBI, Bethesda, MD

1989-1990       Senior Staff Fellow, Pulmonary Branch, NHLBI, Bethesda, MD

1988-1998       NHLBI Alpha-1-Antitrypsin Deficiency Registry Steering Committee

1988-1998       Director, National Alpha-1-Antitrypsin Phenotyping Laboratory, Pulmonary-Critical Care Medicine Branch, NHLBI, Bethesda, MD

1990-1994       NICHD-IRB Committee Member, Bethesda, MD

1995-1998       Head, Unit on Genetic Disorders of Secreted Proteins, Human Genetics Branch, NICHD, Bethesda, MD

1995-1998       Senior Investigator and Head, Pulmonary Function Laboratory, Pulmonary-Critical Care Medicine Branch, NHLBI, Bethesda, MD

1996-2001       Board of Directors & Director of Research Alpha-1 Foundation, Coconut Grove, FL

1996-2002       Co-Chair, Alpha-1 Foundation Medical and Scientific Advisory Committee, Coconut Grove, FL

1998-               Professor of Medicine, Molecular Genetics and Microbiology, Division of Pulmonary and Critical Care Medicine, University of Florida College of Med, Gainesville, FL

1998-               Director, UF Alpha-1 Antitrypsin Genetics Laboratory, University of Florida College of Medicine, Gainesville, FL

2000-10            University of Florida GCRC Associate Director, Gainesville, FL

2006-09            FDA Pulmonary Drug Advisory Committee Chair

2010-17            Chief, Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida College of Medicine, Gainesville, FL

2016-               Vice Chair of Research, Department of Medicine, University of Florida College of Medicine, Gainesville, FL

 

Honors:

1999 –       Alpha-1 Foundation Endowed Professor

2007         UF Faculty Achievement Award

2008         UF Faculty Research Prize in Clinical Science

2010         FDA Service Award

 

Contribution to Science

  1. Pulmonary Fibrosis: My work has been primarily focused on genetic models of Pulmonary Fibrosis and Pulmonary Fibrosis treatment studies.
  2. a. Brantly ML, Rouhani FN, Markello TC, Helip-Wooley A, O’Brien K, Hess R, Huizing M, Gahl WA, Gochuico BR. Alveolar macrophage dysregulation in Hermansky-Pudlak syndrome type 1 Am J Respir Crit Care Med. 2009 Dec 1;180(11):1114-21. doi: 10.1164/rccm.200901-0023OC. Epub 2009 Sep 3. PMID: 19729668
  3. Brantly M, Avila NA, Shotelersuk V, Lucero C, Huizing M, Gahl WA. Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky-Pudlak syndrome, due to mutations in HPS-1.Chest. 2000 Jan;117(1):129-36. PMID: 10631210
  4. Gahl WA, Brantly M, Troendle J, Avila NA, Padua A, Montalvo C, Cardona H, Calis KA, Gochuico B.

Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome.Mol Genet Metab. 2002 Jul;76(3):234-42. PMID: 12126938

  1. Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, Duffy LF, Kuehl EM, Troendle J, Bernardini I. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). N Engl J Med. 1998 Apr 30;338(18):1258-64.

PMID: 9562579

  1. Molecular Basis of Alpha-1-Antitrypsin Deficiency: My work has focused on structure, function and trafficking of mutant forms of alpha-1-antitrypsin.
  2. a. Brantly M, Courtney M, Crystal RG. Repair of the secretion defect in the Z form of alpha 1-antitrypsin by addition of a second mutation. 1988 Dec 23;242(4886):1700-2. PMID: 2904702
  3. Novoradovskaya N, Lee J, Yu ZX, Ferrans VJ, Brantly M. Inhibition of intracellular degradation increases secretion of a mutant form of alpha1-antitrypsin associated with profound deficiency. J Clin Invest. 1998 Jun 15;101(12):2693-701. PMID: 9637703
  4. Lee J, Novoradovskaya N, Rundquist B, Redwine J, Saltini C, Brantly M. Alpha 1-antitrypsin nonsense mutation associated with a retained truncated protein and reduced mRNA.Mol Genet Metab. 1998 Apr;63(4):270-80. PMID: 9635295
  5. Laubach VE, Ryan WJ, Brantly M. Characterization of a human alpha 1-antitrypsin null allele involving aberrant mRNA splicing. Hum Mol Genet. 1993 Jul;2(7):1001-5. PMID: 8364536
  6. Spencer LT, Humphries JE, Brantly ML Antibody response to aerosolized transgenic human alpha1-antitrypsin. N Engl J Med. 2005 May 12;352(19):2030-1. No abstract available.

PMID: 15888711

  1. Alpha-1-Antitrypsin Gene Therapy: My work as been focused on human and animal models of gene therapy for alpha-1-antitrypsin deficiency.
  2. Brantly ML, Spencer LT, Humphries M, Conlon TJ, Spencer CT, Poirier A, Garlington W, Baker D, Song S, Berns KI, Muzyczka N, Snyder RO, Byrne BJ, Flotte TR. Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults.

Hum Gene Ther. 2006 Dec;17(12):1177-86.

PMID: 17115945

  1. Flotte TR, Brantly ML, Spencer LT, Byrne BJ, Spencer CT, Baker DJ, Humphries M.

Phase I trial of intramuscular injection of a recombinant adeno-associated virus alpha 1-antitrypsin (rAAV2-CB-hAAT) gene vector to AAT-deficient adults.Hum Gene Ther. 2004 Jan;15(1):93-128. PMID: 14965381

  1. Brantly ML, Chulay JD, Wang L, Mueller C, Humphries M, Spencer LT, Rouhani F, Conlon TJ, Calcedo R, Betts MR, Spencer C, Byrne BJ, Wilson JM, Flotte TR.Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy.Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16363-8. doi: 10.1073/pnas.0904514106. Epub 2009 Aug 12. Erratum in: Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17606. PMID: 19706466
  2. Mueller C, Chulay JD, Trapnell BC, Humphries M, Carey B, Sandhaus RA, McElvaney NG, Messina L, Tang Q, Rouhani FN, Campbell-Thompson M, Fu AD, Yachnis A, Knop DR, Ye GJ, Brantly M, Calcedo R, Somanathan S, Richman LP, Vonderheide RH, Hulme MA, Brusko TM, Wilson JM, Flotte TR. Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression. J Clin Invest. 2013 Dec;123(12):5310-8. doi: 10.1172/JCI70314. Epub 2013 Nov 15.

PMID: 24231351

Full list of publications http://www.ncbi.nlm.nih.gov/sites/myncbi/mark.brantly.1/bibliography/44608324/public/?sort=date&direction=ascending

 

Research Support

Ongoing:

Granting Agency: Inhibrx 101 LP
Role:                                        Principal Investigator
Title:                      An Open-Label, Multicenter, Phase 1 Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Intravenous Doses of Inhibrx rhAAT-Fc (INBRX-101) in Adults with Alpha-1 Antitrypsin Deficiency (AATD)
Duration:                                 1/1/2018-12/31/2019
Major Goals:         To assess the safety and tolerability of Inhibrx rhAAT-Fc (INBRX-101) administered via intravenous (IV) infusion at escalating dose levels in adults with AATD
 
Granting Agency: Adverum Biotechnologies, Inc.
Role:                                        Principal Investigator
Title:                      Phase 1/2 Study of Intravenous or Intrapleural Administration of a Serotype rh.10 Replication Deficient Adeno-associated Virus Gene Transfer Vector Expressing the Human Alpha-1 Antitrypsin cDNA to Individuals with Alpha-1 Antitrypsin Deficiency
Duration:                                 1/1/2018-12/31/2019
Major Goals:         Determine the safety of ADVM-043 following intravenous administration
 
Granting Agency: Kamada, LTD.
Role:                                        Principal Investigator
Title:                      Follow up, surveillance study on patients who were exposed to inhaled AAT during the Kamada-AAT (inhaled)-006 study
Duration:                                 1/1/2018-12/31/2018
Major Goals:         To follow up on the current health status of patients exposed previously to inhaled AAT, to evaluate the current status of anti-drug antibodies (ADAs) and neutralizing anti-drug
antibodies (nADAs), and to assess the trough AAT levels in patients who are currently receiving AAT IV augmentation therapy and test positive for anti- drug antibodies
Granting Agency:        Alpha-1 Foundation Research Professorship/Fernandez Liver Research Grant
Role:                                        Principal Investigator
Title:                                        Research Endowment/4PBA Mediated Alpha-1 Antitrypsin Secretion Rescue
Duration:                                 12/8/1998-3/31/17
Major Goals:         General support for AAT research program/Phase II Study to evaluate the small molecules and chemical chaperone therapy in AAT deficient subjects
Granting Agency:        Alpha-1 Foundation
Role:                                        Principal Investigator
Title:                      Alpha-1 Foundation Tissue Bank
Duration:                                 7/1/2004-6/30/19
Major Goals:         to provide an Alpha-1 DNA and Tissue Bank for research investigators
Granting Agency:        Grifols
Role:                                        Principal Investigator
Title:                      National AAT Screening Program
Duration:                                 7/1/2000-12/31/18
Major Goals:         Testing for AAT Deficiency and establishment of AAT deficiency-specific
Granting Agency: NIH NCRR/Cincinnati Children’s Hospital Medical Center/LAM Foundation
Role:                                        Site Principal Investigator
Title:                      Quantitative Chest Computed Tomography Unmasking Emphysema Progression in Alpha-1 Antitrypsin Deficiency
Duration:                                 11/1/07-6/30/17
Major Goals:               To investigate longitudinal evaluation of AAT deficient individuals using CT densitometry

 

Completed:

Granting Agency: Kamada, LTD.
Role:                                        Principal Investigator
Title:                      Phase II Randomized Double-Blind Comparison of Aerosolized Alpha-1 Proteinase Inhibitor (Kamada-API)
Duration:                                 4/23/13-1/1/17
Major Goals:         Determine if aerosolized AAT decrease inflammatory factors in the lung of alpha-1-antitrypsin deficient subjects
 
Granting Agency:        Alpha-1 Foundation / HHS-State of Florida / HICL
Role:                                        Principal Investigator
Title:                      ACT program/ HICL AAT Screening Program
Duration:                                 7/1/2000-6/31/2016
Major Goals:         Testing for AAT Deficiency and establishment of AAT deficiency-specific
 
Granting Agency: University of Florida Physicians Clinical Practices Association (FCPA)
Role:                                        Principal Investigator
Title:                      Alpha-1 Antitrypsin Deficiency: Understanding and Identifying. Does a Short Video Improve Physician Understanding and Increase Testing?
Duration:                                 8/1/2016-7/31/2016
Major Goals:         To develop a short video that educates, provides examples, and demonstrates testing for AATD. To pilot-test the acceptance and effectiveness of this type of educational intervention among internal medicine and family medicine residents.
 
Granting Agency: InterMune, Inc.
Role:                                        Principal Investigator
Title:                                        Randomized, Double-blind, Placebo Controlled, Phase 3 study of the Safety and Efficacy of                                                                        Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis
Duration:                                 5/22/06-12/30/14
Major Goals:         To investigate the continued safety of pirfenidone in IPF patients who have completed the Phase 3 study
Granting Agency: Applied Genetics Tech Corporation
Role:                                        Principal Investigator
Title:                      Preclinical and Phase I/II Trials of AAV1-AAT Vectors
Duration:                                 5/1/05-12/22/13
Major Goals:         To test Phase I-II dose escalation of AAV-AAT in AAT deficient individuals to determine safety and dosage necessary for adequate augmentation
Granting Agency: NIH NCRR/Cincinnati Children’s Hospital Medical Center/LAM Foundation
Role:                                        Site Principal Investigator
Title:                      The Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) Trial
Duration:                                 11/1/07-6/30/2010
Major Goals:               To test the safety and efficacy of sirolimus (Rapamycin) in patients with
Lymphangioleiomyomatosis
 
Granting Agency:        NIH/NIHLBI
Role:                                        Principal Investigator
Title:                                        The Anti-Inflammatory Role of Alpha-1 Antitrypsin in the Lung (K24-HL004456)
Duration:                                 3/30/01-7/21/07
Major Goals:         Salary award to support translational researchers who mentor young investigators.  The central project of the grant is to evaluate the role of alpha-1-antitrypsin as anti-inflammatory molecule in subject with AAT deficiency by aerosolizing AAT to the lower respiratory tract.
Granting Agency:  Florida Department of Health
Role:                                        Co-Investigator
Title:                                        Tobacco Smoke-Induced Cell Injury in Lung Compartments
Duration:                                 8/1/04-3/31/08
Major Goals:         To investigate the role of tobacco smoke (TS) in the induction of AM mediated inflammation

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Personnel

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Xichehng Fan, MD, PHD

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Stepfanie Lam

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Jungnam Lee

 

Regina Oshins

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Tammy Flagg

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Nazli Khodayari, PHD

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Mariana Kirst, PHD, M.Sci

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Yuanging Lu, MD

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Emily Mak

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Rejean Liqun Wang, MD, PHD., M.Sci

 

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