Brad Johnson, MD, PhD
Assistant Professor, Dept of Pathology and Laboratory Medicine

Cancer Biology Program

Address

405A Stellar-Chance Labs
422 Curie Blvd
Philadelphia, PA 19104

Office tel.: 215 573-5037
Lab tel.: 215 573-6529
Fax: 215 573-6317
E-mail: johnsonb@mail.med.upenn.edu


EDUCATION

Yale University: BS (Molecular Biophysics and Biochemistry), 1987.

Stanford Medical School: PhD (Biochemistry), 1995.

Stanford Medical School: MD, 1995.

MIT: Postdoctoral Research (Aging Biology), 2001.

RESEARCH INTERESTS

• Molecular biology of aging, Werner syndrome, telomeres,
  recombination.

Key words: Aging, telomeres, recombination, Werner syndrome, cancer, yeast, mice.

Search PubMed for articles

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 their location at these termini 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 RecQ family DNA helicases in coordinating recombination-dependent mechanisms to 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, DNA recombination and transcription in vivo. Most of our studies are being pursued in yeast, because they provide an ideal system in which to study the functions of these fascinating structures. Bioinformatics approaches to understanding G-quadruplex function are also being carried out in collaboration with the laboratory of Dr. Li-San Wang (Department of Pathology and Laboratory Medicine, and PCBI).

A third focus of the lab is to use the mouse model lacking telomerase and the Werner gene that we generated and characterized several years ago to learn more about the mechanisms by which telomere dysfunction contributes to age-related pathology. We are also investigating how transplantation of normal bone marrow rescues degenerative phenotypes in these mice, including gastrointestinal pathology. In addition, we are pursuing collaborative work with the laboratory of Dr. Robert Pignolo (Department of Medicine) to better understand how osteoblast senescence and dysfunction contributes to osteoporosis in these mice.

RECENT PUBLICATIONS

Azam, M, Lee, J.Y., Abraham, V., Chanoux, R., Shoenly, K and Johnson, F.B. (2006). Evidence that the S. cerevisiae Sgs1 protein facilitates recombinational repair of telomeres during senescence. Nucleic Acids Res. 34(2): 506-516.

Turaga RV, Massip L, Chavez A, Johnson FB, Lebel M. (2007). Werner syndrome protein prevents DNA breaks upon chromatin structure alteration. Aging Cell 65(4), 471-81.

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

Pignolo, RJ, Suda, RK, McMillan, EA, Shen, J, Choi, Y, Wright, AC and Johnson, FB. (2008). Defects in Telomere Maintenance Molecules Impair Osteoblast Differentiation and Promote Osteoporosis. Aging Cell, 7(1): 23-31.

Hershman SG, Chen Q, Lee JY, Kozak ML, Yue P, Wang LS, Johnson FB. (2008). Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae. Nucleic Acids Res. 36(1):144-56..

Lab

Rotation Projects

Dr. Johnson is available to discuss possible rotation projects with interested students.

Lab personnel:

Qijun Chen, PhD., Research Specialist
Jamel Johnson, PhD., Postdoctoral Fellow
Marina Kozak, CAMB graduate student
Jasmine Smith, CAMB graduate student
Alex Chavez, CAMB MSTP student
Vanessa George, undergraduate
Glennis Logsdon, undergradurate
Vishesh Agrawal, undergraduate
Lara Abramowitz, CAMB rotation student