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Sudha Sharma
Title Dr
Faculty Rank Associate Professor
Degree PhD
Institution Howard University
Department Biochemistry and Molecular Biology
Clusters Cancer
Genes and Environmental Health/Toxicology
Address
520 W Street NW
Suite 3424D, Adams Bldg
College of Medicine
City Washington
State DC
Postal Code 20059
Telephone 202-806-9750
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  My lab is interested in understanding how mammalian cells maintain genomic stability under normal growth conditions and following DNA damage, and how loss of genetic integrity contributes to cancer, premature aging and other diseases. We utilize a combination of biochemical, molecular and cell biological tools to examine functions of RecQ helicases, a group of highly conserved DNA unwinding enzymes described as caretakers of the genome and implicated in rare genetic diseases. For the past few years, my lab has been investigating investigating RECQ1 (also known as RECQL or RECQL1), the most abundant human RecQ homolog, with a goal to determine common and specialized functions of human RecQ helicases in mechanisms of genome maintenance. The overall focus is on elucidating how impaired function of a specific RecQ protein relates to disease outcomes, including cancer predisposition and premature aging. Following my earlier discovery that the loss of RECQ1 is sufficient to cause genomic instability in mammalian cells, recent work in my lab is investigating in detail the specific roles of RECQ1 in genome maintenance mechanisms of DNA repair and transcriptional regulation, and exploring its broader significance in cellular homeostasis. RECQ1 is frequently upregulated in various cancers and is especially important for cancer cell proliferation. Additionally, germline mutations in RECQ1 significantly increase susceptibility to breast cancer. Thus, we are also investigating RECQ1 as a modifier of cancer development, progression and chemotherapeutic response.

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1. Li XL, Subramanian M, Jones MF, Chaudhary R, Singh DK, Zong X, Gryder B, Sindri S, Mo M, Schetter A, Wen X, Parvathaneni S, Kazandjian D, Jenkins LM, Tang W, Elloumi F, Martindale JL, Huarte M, Zhu Y, Robles AI, Frier SM, Rigo F, Cam M, Ambs S, Sharma S, Harris CC, Dasso M, Prasanth KV, Lal A. Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer. Cell Rep. 2017 Sep 05; 20(10):2408-2423.
2. Parvathaneni S, Lu X, Chaudhary R, Lal A, Madhusudan S, Sharma S. RECQ1 expression is upregulated in response to DNA damage and in a p53-dependent manner. Oncotarget. 2017 Sep 29; 8(44):75924-75942.
3. Woodrick J, Gupta S, Camacho S, Parvathaneni S, Choudhury S, Cheema A, Bai Y, Khatkar P, Erkizan HV, Sami F, Su Y, Schärer OD, Sharma S, Roy R. A new sub-pathway of long-patch base excision repair involving 5' gap formation. EMBO J. 2017 06 01; 36(11):1605-1622.
4. Arora A, Parvathaneni S, Aleskandarany MA, Agarwal D, Ali R, Abdel-Fatah T, Green AR, Ball GR, Rakha EA, Ellis IO, Sharma S, Madhusudan S. Clinicopathological and Functional Significance of RECQL1 Helicase in Sporadic Breast Cancers. Mol Cancer Ther. 2017 01; 16(1):239-250.
5. Sami F, Gary RK, Fang Y, Sharma S. Site-directed mutants of human RECQ1 reveal functional importance of the zinc binding domain. Mutat Res. 2016 08; 790:8-18.
6. Lu X, Parvathaneni S, Li XL, Lal A, Sharma S. Transcriptome guided identification of novel functions of RECQ1 helicase. Methods. 2016 Oct 01; 108:111-7.
7. Sami F, Lu X, Parvathaneni S, Roy R, Gary RK, Sharma S. RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin. Biochem J. 2015 Jun 01; 468(2):227-44.
8. Sharma S. An appraisal of RECQ1 expression in cancer progression. Front Genet. 2014; 5:426.
9. Garige M, Sharma S. Cellular deficiency of Werner syndrome protein or RECQ1 promotes genotoxic potential of hydroquinone and benzo[a]pyrene exposure. Int J Toxicol. 2014 Sep-Oct; 33(5):373-81.
10. Li XL, Lu X, Parvathaneni S, Bilke S, Zhang H, Thangavel S, Vindigni A, Hara T, Zhu Y, Meltzer PS, Lal A, Sharma S. Identification of RECQ1-regulated transcriptome uncovers a role of RECQ1 in regulation of cancer cell migration and invasion. Cell Cycle. 2014; 13(15):2431-45.
11. Li XL, Hara T, Choi Y, Subramanian M, Francis P, Bilke S, Walker RL, Pineda M, Zhu Y, Yang Y, Luo J, Wakefield LM, Brabletz T, Park BH, Sharma S, Chowdhury D, Meltzer PS, Lal A. A p21-ZEB1 complex inhibits epithelial-mesenchymal transition through the microRNA 183-96-182 cluster. Mol Cell Biol. 2014 Feb; 34(3):533-50.
12. Sami F, Sharma S. Probing Genome Maintenance Functions of human RECQ1. Comput Struct Biotechnol J. 2013; 6:e201303014.
13. Parvathaneni S, Stortchevoi A, Sommers JA, Brosh RM, Sharma S. Human RECQ1 interacts with Ku70/80 and modulates DNA end-joining of double-strand breaks. PLoS One. 2013; 8(5):e62481.
14. Lu X, Parvathaneni S, Hara T, Lal A, Sharma S. Replication stress induces specific enrichment of RECQ1 at common fragile sites FRA3B and FRA16D. Mol Cancer. 2013 Apr 22; 12(1):29.
15. Sharma S, Phatak P, Stortchevoi A, Jasin M, Larocque JR. RECQ1 plays a distinct role in cellular response to oxidative DNA damage. DNA Repair (Amst). 2012 Jun 01; 11(6):537-49.
16. Sharma S. Non-B DNA Secondary Structures and Their Resolution by RecQ Helicases. J Nucleic Acids. 2011; 2011:724215.
17. Suhasini AN, Rawtani NA, Wu Y, Sommers JA, Sharma S, Mosedale G, North PS, Cantor SB, Hickson ID, Brosh RM. Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome. EMBO J. 2011 Feb 16; 30(4):692-705.
18. Sharma S, Brosh RM. Unique and important consequences of RECQ1 deficiency in mammalian cells. Cell Cycle. 2008 Apr 15; 7(8):989-1000.
19. Sharma S, Sommers JA, Brosh RM. Processing of DNA replication and repair intermediates by the concerted action of RecQ helicases and Rad2 structure-specific nucleases. Protein Pept Lett. 2008; 15(1):89-102.
20. Sharma S, Brosh RM. Human RECQ1 is a DNA damage responsive protein required for genotoxic stress resistance and suppression of sister chromatid exchanges. PLoS One. 2007 Dec 12; 2(12):e1297.
21. Gupta R, Sharma S, Sommers JA, Kenny MK, Cantor SB, Brosh RM. FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein A and interacts physically and functionally with the single-stranded DNA-binding protein. Blood. 2007 Oct 01; 110(7):2390-8.
22. Peng M, Litman R, Xie J, Sharma S, Brosh RM, Cantor SB. The FANCJ/MutLalpha interaction is required for correction of the cross-link response in FA-J cells. EMBO J. 2007 Jul 11; 26(13):3238-49.
23. Sharma S. Age-related nonhomologous end joining activity in rat neurons. Brain Res Bull. 2007 Jun 15; 73(1-3):48-54.
24. Sharma S, Stumpo DJ, Balajee AS, Bock CB, Lansdorp PM, Brosh RM, Blackshear PJ. RECQL, a member of the RecQ family of DNA helicases, suppresses chromosomal instability. Mol Cell Biol. 2007 Mar; 27(5):1784-94.
25. Gupta R, Sharma S, Doherty KM, Sommers JA, Cantor SB, Brosh RM. Inhibition of BACH1 (FANCJ) helicase by backbone discontinuity is overcome by increased motor ATPase or length of loading strand. Nucleic Acids Res. 2006; 34(22):6673-83.
26. Sharma S, Doherty KM, Brosh RM. Mechanisms of RecQ helicases in pathways of DNA metabolism and maintenance of genomic stability. Biochem J. 2006 Sep 15; 398(3):319-37.
27. Doherty KM, Sharma S, Gupta R, Brosh RM. Tetraplex binding molecules as anti-cancer agents. Recent Pat Anticancer Drug Discov. 2006 Jun; 1(2):185-200.
28. Muftuoglu M, Sharma S, Thorslund T, Stevnsner T, Soerensen MM, Brosh RM, Bohr VA. Cockayne syndrome group B protein has novel strand annealing and exchange activities. Nucleic Acids Res. 2006; 34(1):295-304.
29. Brosh RM, Sharma S. Biochemical assays for the characterization of DNA helicases. Methods Mol Biol. 2006; 314:397-415.
30. Sharma S, Sommers JA, Gary RK, Friedrich-Heineken E, Hübscher U, Brosh RM. The interaction site of Flap Endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA. Nucleic Acids Res. 2005; 33(21):6769-81.
31. Sharma S, Sommers JA, Choudhary S, Faulkner JK, Cui S, Andreoli L, Muzzolini L, Vindigni A, Brosh RM. Biochemical analysis of the DNA unwinding and strand annealing activities catalyzed by human RECQ1. J Biol Chem. 2005 Jul 29; 280(30):28072-84.
32. Doherty KM, Sharma S, Uzdilla LA, Wilson TM, Cui S, Vindigni A, Brosh RM. RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination. J Biol Chem. 2005 Jul 29; 280(30):28085-94.
33. Gupta R, Sharma S, Sommers JA, Jin Z, Cantor SB, Brosh RM. Analysis of the DNA substrate specificity of the human BACH1 helicase associated with breast cancer. J Biol Chem. 2005 Jul 08; 280(27):25450-60.
34. Sharma S, Doherty KM, Brosh RM. DNA helicases as targets for anti-cancer drugs. Curr Med Chem Anticancer Agents. 2005 May; 5(3):183-99.
35. Sommers JA, Sharma S, Doherty KM, Karmakar P, Yang Q, Kenny MK, Harris CC, Brosh RM. p53 modulates RPA-dependent and RPA-independent WRN helicase activity. Cancer Res. 2005 Feb 15; 65(4):1223-33.
36. Sharma S, Sommers JA, Brosh RM. In vivo function of the conserved non-catalytic domain of Werner syndrome helicase in DNA replication. Hum Mol Genet. 2004 Oct 01; 13(19):2247-61.
37. Sharma S, Sommers JA, Wu L, Bohr VA, Hickson ID, Brosh RM. Stimulation of flap endonuclease-1 by the Bloom's syndrome protein. J Biol Chem. 2004 Mar 12; 279(11):9847-56.
38. Sharma S, Otterlei M, Sommers JA, Driscoll HC, Dianov GL, Kao HI, Bambara RA, Brosh RM. WRN helicase and FEN-1 form a complex upon replication arrest and together process branchmigrating DNA structures associated with the replication fork. Mol Biol Cell. 2004 Feb; 15(2):734-50.
39. Sharma S, Sommers JA, Driscoll HC, Uzdilla L, Wilson TM, Brosh RM. The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein. J Biol Chem. 2003 Jun 27; 278(26):23487-96.
40. Rathaur S, Sharma S, Singh RN, Henkle K, Selkirk ME. Antibody responses of Wuchereria bancrofti patients to recombinant Brugia pahangi superoxide dismutase. Indian J Exp Biol. 2001 Jan; 39(1):35-40.
41. Sharma S, Sharma M, Rathaur S. Bancroftian filariasis in the Varanasi region of north India: an epidemiological study. Ann Trop Med Parasitol. 1999 Jun; 93(4):379-87.
42. Sharma S, Rathaur S. Characterization of secretory acetylcholinesterase from Setaria cervi microfilariae: a potential antigen for diagnosis of human filariasis. Trop Med Int Health. 1999 May; 4(5):341-8.
43. Sharma S, Misra S, Rathaur S. Secretory acetylcholinesterase of Setaria cervi microfilariae and its antigenic cross-reactivity with Wuchereria bancrofti. Trop Med Int Health. 1998 Jan; 3(1):46-51.

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