David Mu, Ph.D.

 

Associate Professor

Department of Microbiology and Molecular Cell Biology

Leroy T. Canoles Jr. Cancer Research Center

Harry T. Lester Hall 420
651 Colley Avenue
Norfolk, Virginia 23501
Office: (757) 446-0373
Lab: (757) 446-0527
Email: MuD@evms.edu
Mu CV


 Teaching:

  • Biomedical Sciences Program

Education

  • Ph.D. – University of California at Berkeley
    Adviser: Dr. Judith P. Klinman
  • Postdoctoral Fellow – University of North Carolina at Chapel Hill
    Adviser: Dr. Aziz Sancar

Professional Positions

2012-Present

  • Associate Professor
    Eastern Virginia Medical School
    Department of Microbiology & Molecular Cell Biology

2008 - 2012

  • Associate Professor
    Penn State University College of Medicine
    Departments of Pathology and Biochemistry and Molecular Biology

2004 - 2008

  • Research Investigator
    Cold Spring Harbor Laboratory

1998 - 2004

  • Scientist
    The Cancer Genomics Division, Tularik Inc.

Lab Members

Shao-Chiang Michael Lai, Ph.D., Postdoc

  • Ph.D., SUNY
    Downstate Medical Center
    Brooklyn, NY

Phone: (757) 446-0527

Email: lais@evms.edu
 ‌‌ Kaitlin Helsley, B.S., Research Technician
  • B.S., College of William and Mary
    Williamsburg, VA

Phone: (757) 446-0527

Email: helslekr@evms.edu

 ‌‌‌ Lauren Wood, Ph.D., Postdoc
  • Ph.D., SUNY
    Upstate Medical University
    Syracuse, NY

Phone: (757) 446-0527

Email: woodlw@evms.edu

Cody Phelps, M.S. Graduate Student (for Ph.D.)

  • M.S.
    Eastern Virginia Medical School
    Norfolk, Va

Phone: (757) 446-0527

Email: phelpsca@evms.edu

 

Nicole I. Cox, B.S., Research Master Student

  • B.S., Old Dominion University
    Norfolk, VA

Phone: (757) 446-0527

Email: coxni@evms.edu

 ‌



David Mu, Ph.D. (seated) with his Students and Staff
(Left to Right) Lauren Wood, Michael Lai, Cody Phelps and Kaitlin Helsley


Research Interests

Keywords:  MicroRNA biology, Cancer Research, Lung cancer and biology, Cancer genomics, Molecular study of oncogene mechanism, Oncogenic signaling, Cancer cell metabolism, and Finding new uses of old drugs.

 I. MicroRNAs and mechanism of lung cancer genes

Oncogenes activated via gene amplification have a proven track record of being amenable to invention of new anti-cancer therapies. We and others discovered a recurrent amplified region in lung cancer genomes. This amplicon contains the TTF-1 gene (thyroid transcription factor 1 or known as NKX2-1) which is essential for lung development and morphogenesis. We are interested in mapping the interconnection between TTF-1 and microRNAs to afford novel entry points to investigate TTF-1-linked lung biology. Using a variety of experimental approaches, our laboratory is the first to discover the two types of TTF-1-linked microRNAs – an upstream microRNA that directly regulates TTF-1 expression and downstream microRNAs that are regulated by TTF-1. Currently, we are investigating the biology of these interactions between microRNAs and a lung cancer/development gene.

 

II. New uses of old drugs

In order to minimize the exorbitant costs and risks of de novo drug discovery and development, our strategy is to use off-patent marketed small molecule drugs as the starting point of drug discovery efforts, i.e. repurposing/repositioning an old drug for a new use. Medications that have come off patent are affordable for patients and have well documented biological, toxicological, and pharmacokinetic studies associated with them. Consequently, functional screening of such “old drugs” may readily yield chemicals for immediate clinical trials. Furthermore, “off-label” prescribing allows physicians to innovate with treatments based on emerging research data. Towards this end, we are conducting a multitude of cell-based screens to uncover new utilities of “old drugs” in fighting cancers. This line of research entails a highly translational goal in sight.  Although cancer is the focal point of our work, our approach is in principle transplantable and could be used to discover novel therapeutic strategies to treat other diseases. There are approximately 9990 drugs known to clinical medicine. Each drug should be considered an information-rich entity that merits exploration especially as treatment of orphan diseases.


Publications (peer-reviewed)

53.

Maimon A, Mogilevsky M, Shilo A, Golan-Gerstl R, Obiedat A, Ben-Hur V, Lebenthal-Loinger I, Stein I, Reich R, Beenstock J, Zehorai E, Andersen CL, Thorsen K, Orntoft TF, Davis RJ, Davidson B, Mu D, Karni R.
Mnk2 Alternative Splicing Modulates the p38-MAPK Pathway and Impacts Ras-Induced Transformation. 
Cell Rep. 2014 Apr 24;7(2):501-13. doi: 10.1016/j.celrep.2014.03.041. 10.1016/j.celrep.2014.03.041.
[Epub ahead of print] PubMed PMID: 24726367

52. Mu D.
The Complexity of Thyroid Transcription Factor 1 with Both Pro- and Anti-oncogenic Activities.
J Biol Chem. 2013 Aug 30;288(35):24992-5000. doi: 10.1074/jbc.R113.491647.
Epub 2013 Jul 1. PubMed PMID: 23818522; PubMed Central PMCID: PMC3757165
51. Runkle EA, Mu D.
Tight junction proteins: from barrier to tumorigenesis.
Cancer Lett. 2013 Aug 28;337(1):41-8. doi: 10.1016/j.canlet.2013.05.038.
Epub 2013 Jun 3. PubMed PMID: 23743355; PubMed Central PMCID: PMC3752309
50. Rice SJ, Lai SC, Wood LW, Helsley KR, Runkle EA, Winslow MM, Mu D.
MicroRNA-33a mediates the regulation of high mobility group AT-hook 2 gene (HMGA2) by thyroid transcription factor 1 (TTF-1/NKX2-1).
J Biol Chem. 2013 Jun 7;288(23):16348-60. doi: 10.1074/jbc.M113.474643.
Epub 2013 Apr 26. PubMed PMID: 23625920; PubMed Central PMCID: PMC3675572
49. Cohen-Eliav M, Golan-Gerstl R, Siegfried Z, Andersen CL, Thorsen K, Ørntoft TF, Mu D, Karni R.
The splicing factor SRSF6 is amplified and is an oncoprotein in lung and colon cancers.
J Pathol. 2013 Mar;229(4):630-9. doi: 10.1002/path.4129.
PubMed PMID: 23132731
48. Rajaram M, Zhang J, Wang T, Li J, Kuscu C, Qi H, Kato M, Grubor V, Weil RJ, Helland A, Borrenson-Dale AL, Cho KR, Levine DA, Houghton AN, Wolchok JD, Myeroff L, Markowitz SD, Lowe SW, Zhang M, Krasnitz A, Lucito R, Mu D, Powers RS.
Two Distinct Categories of Focal Deletions in Cancer Genomes.
PLoS One. 2013 Jun 21;8(6):e66264. Print 2013.
PubMed PMID: 23805207; PubMed Central PMCID: PMC3689739
47. Runkle EA, Rice SJ, Qi J, Masser D, Antonetti DA, Winslow MM, Mu D.
Occludin is a direct target of thyroid transcription factor-1 (TTF-1/NKX2-1).
J Biol Chem. 2012 Aug 17;287(34):28790-801. doi: 10.1074/jbc.M112.367987.
Epub 2012 Jul 2. PubMed PMID: 22761434; PubMed Central PMCID: PMC3436544
46. Qi J, Mu D.
MicroRNAs and lung cancers: from pathogenesis to clinical implications.
Front Med. 2012 Jun;6(2):134-55. doi: 10.1007/s11684-012-0188-4.
Epub 2012 Apr 18. Review. PubMed PMID: 22528868; PubMed Central PMCID: PMC3725603
45. Conkrite K, Sundby M, Mu D, Mukai S, MacPherson D.
Cooperation between Rb and Arf in suppressing mouse retinoblastoma.
J Clin Invest. 2012 May 1;122(5):1726-33. doi: 10.1172/JCI61403.
Epub 2012 Apr 9. PubMed PMID: 22484813; PubMed Central PMCID: PMC3336990
44. Qi J, Rice SJ, Salzberg AC, Runkle EA, Liao J, Zander DS, Mu D.
MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1.
Cell Cycle. 2012 Jan 1;11(1):177-86. doi: 10.4161/cc.11.1.18576.
Epub 2012 Jan 1. PubMed PMID: 22185756; PubMed Central PMCID: PMC3272236
43. Conkrite K, Sundby M, Mukai S, Thomson JM, Mu D, Hammond SM, MacPherson D.
miR-17~92 cooperates with RB pathway mutations to promote retinoblastoma.
Genes Dev. 2011 Aug 15;25(16):1734-45. doi: 10.1101/gad.17027411.
Epub 2011 Aug 4. PubMed PMID: 21816922; PubMed Central PMCID: PMC3165937
42. Oliver TG, Mercer KL, Sayles LC, Burke JR, Mendus D, Lovejoy KS, Cheng MH, Subramanian A, Mu D, Powers S, Crowley D, Bronson RT, Whittaker CA, Bhutkar A, Lippard SJ, Golub T, Thomale J, Jacks T, Sweet-Cordero EA.
Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer. Genes Dev. 2010 Apr 15;24(8):837-52. doi: 10.1101/gad.1897010.
PubMed PMID: 20395368; PubMed Central PMCID: PMC2854397
41. Hsu DS, Acharya CR, Balakumaran BS, Riedel RF, Kim MK, Stevenson M, Tuchman S, Mukherjee S, Barry W, Dressman HK, Nevins JR, Powers S, Mu D, Potti A.
Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer.
Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5312-7. doi: 10.1073/pnas.0900827106.
Epub 2009 Mar 11. Erratum in: Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14705. PubMed PMID: 19279207; PubMed Central PMCID: PMC2664027
40. Sangha N, Wu R, Kuick R, Powers S, Mu D, Fiander D, Yuen K, Katabuchi H, Tashiro H, Fearon ER, Cho KR.
Neurofibromin 1 (NF1) defects are common in human ovarian serous carcinomas and co-occur with TP53 mutations. Neoplasia. 2008 Dec;10(12):1362-72, following 1372.
PubMed PMID: 19048115; PubMed Central PMCID: PMC2586687
39. Miao J, Mu D, Ergel B, Singavarapu R, Duan Z, Powers S, Oliva E, Orsulic S.
Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model.
Int J Cancer. 2008 Nov 1;123(9):2041-7. doi: 10.1002/ijc.23726.
PubMed PMID: 18726901; PubMed Central PMCID: PMC2653430
38. Powers S, Mu D.
Genetic similarities between organogenesis and tumorigenesis of the lung.
Cell Cycle. 2008 Jan 15;7(2):200-4.
Epub 2007 Nov 5. Review. PubMed PMID: 18256532
37. Kendall J, Liu Q, Bakleh A, Krasnitz A, Nguyen KC, Lakshmi B, Gerald WL, Powers S, Mu D.
Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer.
Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16663-8.
Epub 2007 Oct 9. PubMed PMID: 17925434; PubMed Central PMCID: PMC2034240
36. Scott CL, Gil J, Hernando E, Teruya-Feldstein J, Narita M, Martínez D, Visakorpi T, Mu D, Cordon-Cardo C, Peters G, Beach D, Lowe SW.
Role of the chromobox protein CBX7 in lymphomagenesis.
Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5389-94.
Epub 2007 Mar 20. PubMed PMID: 17374722; PubMed Central PMCID: PMC1828941
35. Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR.
The gene encoding the splicing factor SF2/ASF is a proto-oncogene.
Nat Struct Mol Biol. 2007 Mar;14(3):185-93.
Epub 2007 Feb 18. PubMed PMID: 17310252
34. MacPherson D, Conkrite K, Tam M, Mukai S, Mu D, Jacks T.
Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification.
EMBO J. 2007 Feb 7;26(3):784-94.
Epub 2007 Jan 18. PubMed PMID: 17235288; PubMed Central PMCID: PMC1794380
33. Pelham RJ, Rodgers L, Hall I, Lucito R, Nguyen KC, Navin N, Hicks J, Mu D, Powers S, Wigler M, Botstein D.
Identification of alterations in DNA copy number in host stromal cells during tumor progression.
Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19848-53.
Epub 2006 Dec 13. PubMed PMID: 17167050; PubMed Central PMCID: PMC1698871
32. Geurts AM, Collier LS, Geurts JL, Oseth LL, Bell ML, Mu D, Lucito R, Godbout SA, Green LE, Lowe SW, Hirsch BA, Leinwand LA, Largaespada DA.
Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers.
PLoS Genet. 2006 Sep 29;2(9):e156.
Epub 2006 Aug 3. PubMed PMID: 17009875; PubMed Central PMCID: PMC1584263
31. Zender L, Spector MS, Xue W, Flemming P, Cordon-Cardo C, Silke J, Fan ST, Luk JM, Wigler M, Hannon GJ, Mu D, Lucito R, Powers S, Lowe SW.
Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach.
Cell. 2006 Jun 30;125(7):1253-67.
PubMed PMID: 16814713; PubMed Central PMCID: PMC3026384
30. Sivertsen EA, Galteland E, Mu D, Holte H, Meza-Zepeda L, Myklebost O, Patzke S, Smeland EB, Stokke T.
Gain of chromosome 6p is an infrequent cause of increased PIM1 expression in B-cell non-Hodgkin's lymphomas. Leukemia. 2006 Mar;20(3):539-42.
PubMed PMID: 16437153
29. Galteland E, Sivertsen EA, Svendsrud DH, Smedshammer L, Kresse SH, Meza-Zepeda LA, Myklebost O, Suo Z, Mu D, Deangelis PM, Stokke T.
Translocation t(14;18) and gain of chromosome 18/BCL2: effects on BCL2 expression and apoptosis in B-cell non-Hodgkin's lymphomas.
Leukemia. 2005 Dec;19(12):2313-23.
PubMed PMID: 16193090
28. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM.
A microRNA polycistron as a potential human oncogene.
Nature. 2005 Jun 9;435(7043):828-33.
PubMed PMID: 15944707
27. Pei L, Wiser O, Slavin A, Mu D, Powers S, Jan LY, Hoey T.
Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function.
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7803-7.
Epub 2003 Jun 2. PubMed PMID: 12782791; PubMed Central PMCID: PMC164668
26. Mu D, Chen L, Zhang X, See LH, Koch CM, Yen C, Tong JJ, Spiegel L, Nguyen KC, Servoss A, Peng Y, Pei L, Marks JR, Lowe S, Hoey T, Jan LY, McCombie WR, Wigler MH, Powers S.
Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene.
Cancer Cell. 2003 Mar;3(3):297-302.
PubMed PMID: 12676587
25. Mu D, Bessho T, Nechev LV, Chen DJ, Harris TM, Hearst JE, Sancar A.
DNA interstrand cross-links induce futile repair synthesis in mammalian cell extracts.
Mol Cell Biol. 2000 Apr;20(7):2446-54.
PubMed PMID: 10713168; PubMed Central PMCID: PMC85433
24. Zhao X, Mu D.
(6-4) photolyase: light-dependent repair of DNA damage.
Histol Histopathol. 1998 Oct;13(4):1179-82. Review.
PubMed PMID: 9810509
23. Bessho T, Mu D, Sancar A.
Initiation of DNA interstrand cross-link repair in humans: the nucleotide excision repair system makes dual incisions 5' to the cross-linked base and removes a 22- to 28-nucleotide-long damage-free strand.
Mol Cell Biol. 1997 Dec;17(12):6822-30.
PubMed PMID: 9372913; PubMed Central PMCID: PMC232538
22. Mu D, Wakasugi M, Hsu DS, Sancar A.
Characterization of reaction intermediates of human excision repair nuclease.
J Biol Chem. 1997 Nov 14;272(46):28971-9.
PubMed PMID: 9360969
21. Mu D, Sancar A.
Model for XPC-independent transcription-coupled repair of pyrimidine dimers in humans.
J Biol Chem. 1997 Mar 21;272(12):7570-3.
PubMed PMID: 9065408
20. Mu D, Tursun M, Duckett DR, Drummond JT, Modrich P, Sancar A.
Recognition and repair of compound DNA lesions (base damage and mismatch) by human mismatch repair and excision repair systems.
Mol Cell Biol. 1997 Feb;17(2):760-9.
PubMed PMID: 9001230; PubMed Central PMCID: PMC231802
19. Mu D, Sancar A.
DNA excision repair assays.
Prog Nucleic Acid Res Mol Biol. 1997;56:63-81. Review.
PubMed PMID: 9187051
18. Reardon JT, Mu D, Sancar A.
Overproduction, purification, and characterization of the XPC subunit of the human DNA repair excision nuclease.
J Biol Chem. 1996 Aug 9;271(32):19451-6.
PubMed PMID: 8702634
17. Zamble DB, Mu D, Reardon JT, Sancar A, Lippard SJ.
Repair of cisplatin--DNA adducts by the mammalian excision nuclease.
Biochemistry. 1996 Aug 6;35(31):10004-13.
PubMed PMID: 8756462
16. Kazantsev A, Mu D, Nichols AF, Zhao X, Linn S, Sancar A.
Functional complementation of xeroderma pigmentosum complementation group E by replication protein A in an in vitro system.
Proc Natl Acad Sci U S A. 1996 May 14;93(10):5014-8.
PubMed PMID: 8643521; PubMed Central PMCID: PMC39398
15. Matsunaga T, Park CH, Bessho T, Mu D, Sancar A.
Replication protein A confers structure-specific endonuclease activities to the XPF-ERCC1 and XPG subunits of human DNA repair excision nuclease.
J Biol Chem. 1996 May 10;271(19):11047-50.
PubMed PMID: 8626644
14. Mu D, Hsu DS, Sancar A.
Reaction mechanism of human DNA repair excision nuclease.
J Biol Chem. 1996 Apr 5;271(14):8285-94.
PubMed PMID: 8626523
13. Matsunaga T, Mu D, Park CH, Reardon JT, Sancar A.
Human DNA repair excision nuclease. Analysis of the roles of the subunits involved in dual incisions by using anti-XPG and anti-ERCC1 antibodies.
J Biol Chem. 1995 Sep 1;270(35):20862-9.
PubMed PMID: 7657672
12. Park CH, Mu D, Reardon JT, Sancar A.
The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor.
J Biol Chem. 1995 Mar 3;270(9):4896-902.
PubMed PMID: 7876263
11. Mu D, Park CH, Matsunaga T, Hsu DS, Reardon JT, Sancar A.
Reconstitution of human DNA repair excision nuclease in a highly defined system.
J Biol Chem. 1995 Feb 10;270(6):2415-8.
PubMed PMID: 7852297
10. Mu D, Klinman JP.
Cloning of mammalian topa quinone-containing enzymes.
Methods Enzymol. 1995;258:114-22.
PubMed PMID: 8524143
09. Mu D, Bertrand-Burggraf E, Huang JC, Fuchs RP, Sancar A, Fuchs BP.
Human and E.coli excinucleases are affected differently by the sequence context of acetylaminofluorene-guanine adduct. Nucleic Acids Res. 1994 Nov 25;22(23):4869-71. Erratum in: Nucleic Acids Res 1995 Feb 11;23(3):540.
PubMed PMID: 7702657; PubMed Central PMCID: PMC523749
08. Mu D, Medzihradszky KF, Adams GW, Mayer P, Hines WM, Burlingame AL, Smith AJ, Cai D, Klinman JP.
Primary structures for a mammalian cellular and serum copper amine oxidase.
J Biol Chem. 1994 Apr 1;269(13):9926-32.
PubMed PMID: 8144587
07. Klinman JP, Mu D.
Quinoenzymes in biology.
Annu Rev Biochem. 1994;63:299-344. Review.
PubMed PMID: 7979241
06. Mu D, Janes SM, Smith AJ, Brown DE, Dooley DM, Klinman JP.
Tyrosine codon corresponds to topa quinone at the active site of copper amine oxidases.
J Biol Chem. 1992 Apr 25;267(12):7979-82.
PubMed PMID: 1569055
05. Brown DE, McGuirl MA, Dooley DM, Janes SM, Mu D, Klinman JP.
The organic functional group in copper-containing amine oxidases. Resonance Raman spectra are consistent with the presence of topa quinone (6-hydroxydopa quinone) in the active site.
J Biol Chem. 1991 Mar 5;266(7):4049-51.
PubMed PMID: 1900285
04. Janes SM, Mu D, Wemmer D, Smith AJ, Kaur S, Maltby D, Burlingame AL, Klinman JP.
A new redox cofactor in eukaryotic enzymes: 6-hydroxydopa at the active site of bovine serum amine oxidase.
Science. 1990 May 25;248(4958):981-7.
PubMed PMID: 2111581
03. Tsing I, Mu D, Lee G, Peng S, Liu R.
Preparation and Properties of Molybdenum-Pentadienyl Complexes: A Facile h5<=>h3 Reversible Interconversion for a Pentadienyl Ligands.
Organometallics. 1989 ; 8:2248-2252
02. Liu F, Mu D, Lee G, Peng S, Liu R.
Preparation of Molybdenum-h3- Pentadienyl Complexes: Structural Characterization of a Delocalized Pentadienyl Ligand in Anti-h3 Geometry.
Organometallics. 1989 ; 8:402-407
01. Lee G, Peng S, Lush S, Mu D, Liu R.
Reaction of iron-.eta.1-dienyl complexes with dienophiles. X-ray structures of the [4 + 2] cycloaddition adducts.
Organometallics. 1988 ; 7:1155–1161

 

 

 

 Patent Applications

1. Amplified cancer gene hepsin.
US Patent application number: 20030049645.
Filed 2/12/2002.
2. AMPLIFIED ONCOGENES AND THEIR INVOLVEMENT IN CANCER.
US Patent application number: 20030092042.
Filed 8/27/2002.
3. AMPLIFICATION AND OVEREXPRESSION OF ONCOGENES.
US Patent application number: 20040005615.
Filed 5/22/2003.
4. GENE AMPLIFICATION AND OVEREXPRESSION IN CANCER. US Patent application number: 20050026194.
Filed 6/15/2004.
5. KCNB: A NOVEL POTASSIUM CHANNEL PROTEIN. US Patent application number: 20080234470.
Filed 1/3/2008.

 Patents Granted

1. Diagnosis and treatment of cancer using mammalian pellino polypeptides and polynucleotides.
United States Patent # 7,115,368, issued 10/3/2006.
2. Nucleic acid encoding KCNB potassium channel.
United States Patent # 7,462,465, issued 12/9/2008.