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F. Bradley Johnson, MD, PhD

F. Bradley Johnson, MD, PhD Physician

Associate Professor of Pathology and Laboratory Medicine
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Dr. Johnson is a Penn Medicine employed physician.

Clinical Specialties

Specialty:

  • Pathology and Laboratory Medicine

Programs & Centers:

Board Certification:

  • Pathology - Clinical Pathology, 2000

Description of Clinical Expertise

HLA and transplantation testing

Practice Locations and Appointments

Insurance Accepted

  • Aetna US Healthcare
  • Cigna
  • Cigna HealthSpring
  • CVS Health
  • Devon Health Services (Americare)
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Medicaid
  • PA Medicare
  • Preferred Health Care/LGH
  • Rail Road Medicare / Palmetto GBA
  • Remedy Partners at Penn Medicine
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan

Education and Training

Medical School: Stanford University School of Medicine
Residency: Brigham and Women's Hospital
Fellowship: Massachusetts Institute of Technology

Memberships

American Federation for Aging Research, National Czech Academy of Sciences (ASCR), International European Research Council, International Evaluation Committee of the French National Research Agency (ANR), International Kentucky Science and Engineering Foundation, National NIH Cellular Mechanisms of Aging and Development (CMAD) Study Section., National NIH Cellular Mechanisms of Aging and Development study section, National NIH Molecular Genetics C Study Section, National NIH P01 on DNA Repair, Mutations and Cellular Aging, National NIH Special Emphasis Panel/Scientific Review Group 2008/10 ZRG1 BDA-A (02), National NIH Special Emphasis Panel/Scientific Review Group 2009/10 ZAG1 ZIJ-2 (O5), National University of Michigan Geriatrics Center Pilot Grant Program, National

Hospital Affiliation

Dr. Johnson is a Penn Medicine employed physician.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.
  • Penn Presbyterian Medical Center: Has privileges to treat patients in the hospital.
  • Pennsylvania Hospital: Has privileges to treat patients in the hospital.

Research

Description of Research Expertise:

Research Interests
Molecular biology of aging, cell senescence, Werner syndrome, telomeres,
recombination, G-quadruplexes, neurodegeneration, transplantation.

Key words: Aging, telomeres, recombination, Werner syndrome, cancer, yeast, mice, G-quadruplex, neurodegeneration, transplantation.

Description of Research
Our lab is interested in the biology of human aging and cancer, and we are focusing particularly on how they are influenced by telomere maintenance and dysfunction. Telomeres are the structures that cap the ends of chromosomes, and this location makes them critical for genome stability as well as particularly susceptible themselves to a variety of insults including oxidative damage, exonucleolytic attack, and inappropriate processing by recombination factors.

One focus of the lab is to investigate mechanisms of telomere maintenance. We have identified roles for the RecQ family DNA helicases in coordinating recombination-dependent mechanisms that maintain telomeres. This family of helicases includes those that are deficient in the Werner and Bloom syndromes, which are diseases characterized by premature aging and elevated rates of cancer. Our findings in mice and yeast have helped establish telomere defects as an important cause of the clinical phenotypes observed in these syndromes. More recently, we have also begun exploring roles for chromatin regulatory factors, including SUMO modifiers and regulators of histone acetylation, in telomere maintenance. We hope that by better understanding how RecQ helicases and chromatin factors maintain telomeres, new methods for preserving telomere function in normal tissues and for disrupting telomere function in malignancies may be developed.

A second focus of the lab is to investigate the biology of G-quadruplexes, which are four-stranded DNA structures formed by G-rich sequences like telomeres. The RecQ family of helicases, including WRN and BLM, are particularly adept at unwinding G-quadruplexes. Recently, we have obtained evidence that G-quadruplexes regulate telomere capping, cell senescence, DNA recombination and transcription in vivo. Cell biologic, bioinformatic and structural approaches to understanding G-quadruplex function are being pursued.

A third focus of the lab is to use a mouse model lacking telomerase to learn more about the mechanisms by which telomere dysfunction contributes to age-related pathology. We are investigating how transplantation of normal bone marrow and manipulation of the Wnt pathway rescues this and other degenerative phenotypes in these mice.

A fourth interest of the lab is the measurement in human clinical specimens of telomere lengths and capping, telomerase activity, chromatin regulators, and cell senescence. We are particularly interested in understanding how these factors contribute to age-related neurodegenerative diseases and the success of transplanted tissues.

Rotation Projects
Please contact Dr. Johnson to discuss potential rotation projects.

Lab Personnel
Qijun Chen, PhD, Research Specialist
Jay Johnson, PhD, Research Associate
Jen Wanat, PhD, Postdoc
Jesse Platt, MD-PhD student
Ting Yang, MD-PhD student
Becky Billmire, PhD student
Jordan Driskill, Undergraduate
Rebecca Duncan, School of Nursing
Shufei Song, PhD student

Selected Publications:

Jesse M. Platt, Paul Ryvkin, Jennifer J. Wanat, Greg Donahue, M. Dan Ricketts, Steven P. Barrett, Hannah J. Waters, Shufei Song, Alejandro Chavez, Khaled Omar Abdallah, Stephen R. Master, Li-San Wang, F. Brad Johnson: Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence. Genes and Development 27 (12): 1406-20,2013.

Smith Jasmine S, Chen Qijun, Yatsunyk Liliya A, Nicoludis John M, Garcia Mark S, Kranaster Ramon, Balasubramanian Shankar, Monchaud David, Teulade-Fichou Marie-Paule, Abramowitz Lara, Schultz David C, Johnson F Brad: Rudimentary G-quadruplex-based telomere capping in Saccharomyces cerevisiae. Nature Structural & Molecular Biology 18 (4): 478-85,2011.

Chavez Alejandro, Agrawal Vishesh, Johnson F Brad: Homologous recombination-dependent rescue of deficiency in the structural maintenance of chromosomes (Smc) 5/6 complex. The Journal of Biological Chemistry 286 (7): 5119-25,2011.

Kozak, ML, Chavez, A, Dang, W, Berger, SL, Ashok, A, Guo, X, and Johnson, FB.: Inactivation of the Sas2 histone acetyltransferase delays senescence driven by telomere dysfunction. EMBO Journal 29 (1): 158-70,2010.

J.N. Lukens, V. Van Deerlin, C.M. Clark, S.X. Xie, and F.B. Johnson: Comparisons of telomere lengths in peripheral blood and cerebellum in Alzheimer's disease Alzheimer's and Dementia 5 (6): 463-9,2009.

Johnson, JE, Cao, K, Ryvkin, P, Wang, L-S, and Johnson, FB: Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential. Nucleic Acids Research 38 (4): 1114-1142,2010.

Chavez Alejandro, George Vanessa, Agrawal Vishesh, Johnson F Brad: Sumoylation and the structural maintenance of chromosomes (Smc) 5/6 complex slow senescence through recombination intermediate resolution. The Journal of biological chemistry 285 (16): 11922-30,2010.

Lee JY, Kozak M, Martin JD, Pennock E, Johnson FB.: Evidence That a RecQ Helicase Slows Senescence by Resolving Recombining Telomeres. PLOS Biology 5 (6): e160,2007.

Marciniak, R.A., Cavasos, D., Montellano, R., Chen, Q., Guarente, L., and Johnson, F.B.: A novel telomere structure in a human ALT cell line. Cancer Res. 65 (7): 2730-7,2005.

Du, X., Shen, J., Kugan, N., Furth, E.E., Lombard, D.B., Cheung, C., Pak, S., Luo, G., Pignolo, R.J., Guarente, L, and Johnson, F.B.: Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol. Cell. Biol. 24 (19): 8437-8446,2004.

View all publications

Academic Contact Info

Department of Pathology and Laboratory Medicine
Stellar Chance, 405A
422 Curie Blvd.
University of Pennsylvania

Philadelphia, PA 19104-6100
Phone: (215) 573-5037
Fax: (215) 573-6317

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