Steven A. Akman, M.D.

Professor, Internal Medicine and Cancer Biology

Email: sakman@wfubmc.edu

Education:

AB in physics, Cornell University, 1971

MD, Albert Einstein, 1975

Post doctoral fellow in the laboratory of Clinical Biochemistry, DCT, NCI, 1978 - 1980

Board Certification:

Internal Medicine, 1978

Medical Oncology, 1981

Research Interests:

The Akman lab is interested in DNA damage, mutagenesis, and genomic instability.  We use a human cell mutation reporting plasmid in which to site-specifically place chemically synthesized DNA base adducts in the tRNA gene supF.  These constructs allow us to analyze the biology of specific well characterized DNA base adducts with regard to their mutagenic potential and modes of repair.  Currently, we are studying N2-ethyl and isopropyl deoxyguanosine and N6-isopropyl deoxyadenosine adducts that result from exposure of DNA to alkylating carcinogens.

Additionally, in collaboration with the Vaughn lab we are interested in the role of unusual non-Watson-Crick DNA structures in fostering genomic instability.  We have identified, purified, and expressed an enzyme from rapidly replicating human cells that recognizes and resolves Hoogsteen bonded quadruplex DNA.  We are currently exploring the biologic roles of this enzyme in: (1) maintaining genomic stability of polydeoxyguanidylate containing regions of DNA, e.g., the telomere, and (2) modulating transcription of replication-associated genes, e.g., c-myc.

Competition of unlabelled structures in standard G4-DNA resolvase assay shows that recombinant G4-DNA resolvase has approximately 300-fold greater specificity for G4-DNA than potential duplex helicase substrates. a, An illustrative G4-DNA resolvase assay on non-denaturing PAGE with increasing amounts of unlabelled competing DNA structures. Lanes 1-7 correspond to 0, equimolar, 3-fold, 10-fold, 30-fold, 100-fold, or 300-fold molar excess of unlabelled competitor, respectively. b, Graphic representation of change in G4-DNA resolvase activity caused by unlabelled competitors (Mean ± S.D. of percent change in activity compared to no competitor, reactions set up in triplicate; S.D. < 1% in all cases). Percent of activity is measured by the amount of monomer produced with competitor normalized to amount of monomer formed without competitor.

Current Projects:

Studying the biology of exocyclic alkylamino purine DNA adducts.  Studying resolution of quadruplex DNA

Publications:

Akman SA, Okcu SC, Halicioğlu O, Sutcuoglu S, Anil M, Kizilgunesler A, Bakiler AR.  Therapeutic efficacy of sequential and simultaneous treatments with interferon-alpha and lamivudine in children with chronic hepatitis B. Pediatr Int. 2007 Dec;49(6):848-52.

Gajewski E, Gaur S, Akman SA, Matsumoto L, van Balgooy JN, Doroshow JH.

Oxidative DNA base damage in MCF-10A breast epithelial cells at clinically achievable concentrations of doxorubicin.

Biochem Pharmacol. 2007 Jun 15;73(12):1947-56. Epub 2007 Mar 24.

Akman SA. Replication of N2-Ethyldeoxyguanosine DNA Adducts in the Human Embryonic Kidney Cell Line 23 Volume 19, Number 7, July, 2006, pp 960-967. Chem Res Toxicol. 2007 Jan;20(1):164.

Upton DC, Wang X, Blans P, Perrino FW, Fishbein JC, and Akman SA.: Mutagenesis by exocyclic alkylamino purine adducts in Escherichia coli. Mutat. Res. 2006 Jul 25;599(1-2):1-10.

Upton DC, Wang X, Blans P, Perrino FW, Fishbein, JC, Akman SA. Replication of n2-ethyldeoxyguanosine DNA adducts in the human embryonic kidney cell line 293. Chem Res Toxicol. 2006 Jul;19(7):960-7.

Publications:
For a listing of additional publications, refer to PubMed, a service provided by the National Library of Medicine