Clinical Research Associate

Ana Paola Cotrim, D.D.S., Ph.D.

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Ana Paola P. Cotrim, DDS, PhD

240-***-**** ********.******@*****.***

Immigration status: USA Citizen

Professional Profile

Extensive experience in the design and development of research protocols, regulatory standards guiding clinical research; experience in investigational new drug (IND) applications and in coordinating teams in the implementation on clinical research projects. Education

2014-16 Masters of Health Sciences in Clinical Research, Duke University School of Medicine, Durham, NC (thesis to be defended)

2003 PhD summa cum laude, Oral Pathology, FOP, UNICAMP, Brazil 1999 MSc summa cum laude, Biology, FOP, UNICAMP, Brazil 1996 DDS Foundation Herminio Ometto, UniAraras, Brazil Employment and Work Experience:

2003-2021 National Institutes of Heath

NCI; research associate on the Laboratory of Genome Integrity NHGRI; research associate with the Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch

NIDCR; Staff Clinician with the Molecular Physiology and Therapeutics Branch Sjögren’s Syndrome

NIDCR; Staff Scientist with the Gene Therapy Section NIDCR; Postdoctoral Research Fellow

Patents:

2012 U.S. Provisional Patent Application No. 61/696,861: Methods of preventing the development of mucositis and related disorders (mTOR) Leadership and Community Service:

2015-2023 troop leader and service unit cookie manager for the Girl,Scouts 2010-2012, Member of the Board of Directors at the Parents of Preschoolers, NIH daycare center

2005 – 2006, FELCOM liaison at NIH Parenting Board 2004 – FELCOM liaison to the NIH Parenting Board

2003 – 2005, NIDCR representative at the NIH FELCOM (Fellows committee) 2002 – 2013, Volunteer as translator (Portuguese, Spanish) at NIH Clinical Center Publications:

1. Paian J, Wu W, Yamada S, Sciascia N, Callen E, Paola Cotrim A, Deshpande R A, Maman Y, Day A, Paull T T, Nussenzweig A. (2020). ATM and PRDM9 regulate SPO11-bound recombination intermediates during meiosis. Nature communications, 11(1), 857. https://doi.org/10.1038/s41467-020-14654-w

Ana Paola Cotrim, D.D.S., Ph.D.

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2. Ferreira JNA, Zheng C, Lombaert IMA, Goldsmith CM, Cotrim AP, Symonds JM, Patel VN, Hoffman MP. Neurturin Gene Therapy Protects Parasympathetic Function to Prevent Irradiation-Induced Murine Salivary Gland Hypofunction. Mol Ther Methods Clin Dev. 2018 Feb 23;9:172-180. doi: 10.1016/j.omtm.2018.02.008.

3. Hu L, Wang Y, Cotrim AP, Zhu Z, Gao R, Zheng C, Goldsmith CM, Jin L, Zhang C, Mitchell JB, Baum BJ, Wang S. Effect of Tempol on the prevention of irradiation-induced mucositis in miniature pigs. Oral Dis. 2017 Sep;23(6):801-808. doi: 10.1111/odi.12667. 4. Corden A, Handelman B, Yin H, Cotrim A, Alevizos I, Chiorini JA. Neutralizing antibodies against adeno- associated viruses in Sjögren's patients: implications for gene therapy. Gene Ther. 2017 Feb 2. doi: 10.1038/gt.2017.1.

5. Alevizos I, Zheng C, Cotrim AP, Liu S, McCullagh L, Billings ME, Goldsmith CM, Tandon M, Helmerhorst EJ, Catalán MA, Danielides SJ, Perez P, Nikolov NP, Chiorini JA, Melvin JE, Oppenheim FG, Illei GG, Baum BJ. - Late responses to adenoviral-mediated transfer of the aquaporin-1 gene for radiation- induced salivary hypofunction. Gene Ther. 2017 Jan 19. 6. Baum BJ, Afione S, Chiorini JA, Cotrim AP, Goldsmith CM, Zheng C. Gene Therapy of Salivary Diseases. Methods Mol Biol. 2017;1537:107-123.

7. Alevizos I, Zheng C, Cotrim AP, Goldsmith CM, McCullagh L, Berkowitz T, Strobl SL, Malyguine A, Kopp WC, Chiorini JA, Nikolov NP, Neely M, Illei GG, Baum BJ. Immune reactivity after adenoviral- mediated aquaporin-1 cDNA transfer to human parotid glands. Oral Dis. 2016 Nov 25. doi: 10.1111/odi.12614

8. Mizrachi A, Cotrim AP, Katabi N, Mitchell JB, Verheij M, Haimovitz-Friedman A. Radiation-Induced Microvascular Injury as a Mechanism of Salivary Gland Hypofunction and Potential Target for Radioprotectors. Radiat Res. 2016 Aug;186(2):189-95. doi: 10.1667/RR14431.1. 9. Teos LY1, Zhang Y, Cotrim AP, Swaim W, Won JH, Ambrus J, Shen L, Bebris L, Grisius M, Jang SI, Yule DI, Ambudkar IS, Alevizos I. - IP3R deficit underlies loss of salivary fluid secretion in Sjögren's Syndrome. Sci Rep. 2015 Sep 14;5:13953. doi: 10.1038/srep13953. 10. Zheng C, Baum BJ, Liu X, Goldsmith CM, Perez P, Jang SI, Cotrim AP, McCullagh L, Ambudkar IS, Alevizos I. Persistence of hAQP1 expression in human salivary gland cells following AdhAQP1 transduction is associated with a lack of methylation of hCMV promoter. Gene Ther. 2015 Jul 16. doi: 10.1038/gt.2015.55.

11. Baum BJ, Alevizos I, Chiorini JA, Cotrim AP, Zheng C. Advances in salivary gland gene therapy - oral and systemic implications. Expert Opin Biol Ther. 2015 Jul 6:1-12. 12. Cotrim AP, Alevizos I. Human and Viral microRNA Expression in Sjögren Syndrome. J Rheumatol. 2014 Nov;41(11):2102-3

13. Guo L, Gao R, Xu J, Jin L, Cotrim AP, Yan X, Zheng C, Goldsmith CM, Shan Z, Hai B, Zhou J, Zhang C, Baum BJ, Wang S. AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine. Gene Ther. 2014 Jul 17. doi: 10.1038/gt.2014.63 14. Han G, Bian L, Li F, Cotrim A, Wang D, Lu J, Deng Y, Bird G, Sowers A, Mitchell JB, Gutkind JS, Zhao R, Raben D, ten Dijke P, Refaeli Y, Zhang Q, Wang XJ. Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis. Nat Med. 2013 Apr;19(4):421-8. doi: 10.1038/nm.3118. Epub 2013 Mar 10.

15. Rocha EM, Cotrim AP, Zheng C, Riveros PP, Baum BJ, Chiorini JA. Recovery of radiation-induced dry eye and corneal damage by pretreatment with adenoviral vector-mediated transfer of erythropoietin to the salivary glands in mice. Hum Gene Ther. 2013 Apr;24(4):417-23. doi: 10.1089/hum.2012.111 16. Xibao Liu, Ana Cotrim, Leyla Teos, Changyu Zheng, William Swaim, James Mitchell, Yasuo Mori & Indu Ambudkar. Loss of TRPM2 function protects against irreversible salivary gland dysfunction following head and neck irradiation. Nature Communications DOI: 10.1038/ncomms2526 17. Sarah M. Knox*, Isabelle M.A. Lombaert*, Candace L. Haddox, Shaun R. Abrams, Adrian J. Wilson, Ana Cotrim & Matthew P. Hoffman. Parasympathetic stimulation improves epithelial organ regeneration. Nature Communications 2013;4:1494. doi: 10.1038/ncomms2493. 18. Eduardo M. Rocha, Ana P. Cotrim, Changyu Zheng, Paola Perez Riveros, Bruce J. Baum, John A. Chiorini. Prevention of radiation-induced dry eye and corneal damage by adenoviral vector-mediated transfer of erythropoietin to the salivary glands in mice. Human Gene Therapy 2013 Apr;24(4):417-23. doi: 10.1089/hum.2012.111.

19. Gangwen Han, Li Bian, Fulun Li, Ana Cotrim, Donna Wang, Jian Bo Lu, Yu Deng, Gregory Bird, Anastasia Sowers, James Mitchell, J. Silvio Gutkind, Rui Zhao, Peter ten Dijke, Yosef Refaeli, Qinghong

Ana Paola Cotrim, D.D.S., Ph.D.

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Zhang, and Xiao-Jing Wang - Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis. Nat Med 2013 Apr;19(4):421-8. doi: 10.1038/nm.3118. 20. Baum BJ, Alevizos I, Zheng C, Cotrim AP, Liu S, McCullagh L, Goldsmith CM, Burbelo PD, Citrin DE, Mitchell JB, Nottingham LK, Rudy SF, Van Waes C, Whatley MA, Brahim JS, Chiorini JA, Danielides S, Turner RJ, Patronas NJ, Chen CC, Nikolov NP, Illei GG. Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction. Proc Natl Acad Sci USA. 2012 Nov 5.

21. Iglesias- Bartolome R, Patel V, Cotrim A, Leelahavanichkul K, Molinolo AA, Mitchell JB, Gutkind, JS. mTOR Inhibition Prevents Epithelial Stem Cell Senescence and Protects from Radiation-Induced Mucositis. Cell Stem Cell. 2012 Sep 7;11(3):401-14. 22. Zheng C, Cotrim AP, Nikolov N, Mineshiba F, Swain W, Baum BJ A novel hybrid adenoviral vector with more extensive E3 deletion extends transgene expression in submandibular galnds. Hum Gene Ther Methods. 2012 Jun 29 PMID: 22746168

23. Cotrim AP, Yoshikawa M, Sunshine AN, Zheng C, Sowers AL, Thetford AD, Cook JA, Mitchell JB, Baum BJ Pharmacological Protection from Radiation Cisplatin-induced Oral Mucositis. Int J Radiat Oncol Biol Phys. 2011 Dec 22.

24. Cotrim A*, Zheng C*, Rowzee A, Swaim W, Sowers A, Mitchell JB, Baum BJ. Prevention of radiation- induced salivary hypofunction following hKGF gene delivery to murine submandibular glands. Clin Cancer Res. 2011;17(9):2842-51.

25. Sumita Y, Liu Y, Khalili S, Maria OM, Xia D, Key S, Cotrim AP, Mezey E, Tran SD. Bone marrow- derived cells rescue salivary gland function in mice with head and neck irradiation. Int J Biochem Cell Biol. 2011;Jan;43(1):80-7.

26. Xu J, Yan X, Gao R, Mao L, Cotrim AP, Zheng C, Zhang C, Baum BJ, Wang S. Effect of irradiation on microvascular endothelial cells of parotid glands in the miniature pig. Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):897-903.

27. Baum BJ, Adriaansen J, Cotrim AP, Goldsmith CM, Perez P, Qi S, Rowzee AM, Zheng C. Gene therapy of salivary diseases. Methods Mol Biol. 2010;666:3-20. 28. Voutetakis A, Cotrim AP, Rowzee A, Zheng C, Rathod T, Yanik T, Loh YP, Baum BJ, Cawley NX. Systemic Delivery of Bioactive Glucagon-Like Peptide 1 after Adenoviral-Mediated Gene Transfer in the Murine Salivary Gland. Endocrinology 2010;151(9):4566-72. 29. Citrin D, Cotrim AP, Hyodo F, Baum BJ, Krishna MC, Mitchell JB. Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist. 2010;15(4):360-71. 30. Zheng C, Voutetakis A, Metzger M, Afione S, Cotrim AP, Eckhaus MA, Rivera VM, Clackson T, Chiorini JA, Donahue RE, Dunbar CE, Baum BJ. Evaluation of a rapamycin-regulated serotype 2 adeno- associated viral vector in macaque parotid glands. Oral Dis. 2010 Apr;16(3):269-77. 31. Zheng C, Nikolov NP, Alevizos I, Cotrim AP, Liu S, McCullagh L, Chiorini JA, Illei GG, Baum BJ. Transient detection of E1-containing adenovirus in saliva after the delivery of a first-generation adenoviral vector to human parotid gland. J Gene Med. 2010 Jan;12(1):3-10. 32. Baum BJ, Zheng C, Alevizos I, Cotrim AP, Liu S, McCullagh L, Goldsmith CM, McDermott N, Chiorini JA, Nikolov NP, Illei GG. Development of a gene transfer-based treatment for radiation-induced salivary hypofunction. Oral Oncol. 2010 Jan;46(1):4-8.

33. Voutetakis A, Zheng C, Cotrim AP, Mineshiba F, Afione S, Roescher N, Swaim WD, Metzger M, Eckhaus MA, Donahue RE, Dunbar CE, Chiorini JA, Baum BJ AAV5-mediated gene transfer to the parotid glands of non-human primates. Gene Ther. 2010 Jan;17(1):50-60. 34. Zheng C*, Cotrim AP*, Sunshine AN, Sugito T, Liu L, Sowers A, Mitchell JB, Baum BJ. Prevention of radiation-induced oral mucositis after adenoviral vector-mediated transfer of the keratinocyte growth factor cDNA to mouse submandibular glands. Clin Cancer Res. 2009 Jul 15;15(14):4641-8. 35. Hai B, Yan X, Voutetakis A, Zheng C, Cotrim AP, Shan Z, Ding G, Zhang C, Xu J, Goldsmith CM, Afione S, Chiorini JA, Baum BJ, Wang S. Long-term transduction of miniature pig parotid glands using serotype 2 adeno-associated viral vectors. J Gene Med. 2009;11(6):506-14. 36. Baum BJ, Zheng C, Cotrim AP, McCullagh L, Goldsmith CM, Brahim JS, Atkinson JC, Turner RJ, Liu S, Nikolov N, Illei G.G. Aquaporin-1 gene transfer to correct radiation-induced salivary hypofunction. Handb Exp Pharmacol. 2009;(190):403-18.

37. Sugito T, Mineshiba F, Zheng C, Cotrim AP, Goldsmith CM, Baum BJ. Transient TWEAK overexpression leads to a general salivary epithelial cell proliferation. Oral Dis. 2009 Jan;15(1):76-81.

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38. Voutetakis A, Zheng C, Metzger M, Cotrim AP, Donahue RE, Dunbar CE, Baum BJ. Sorting of transgenic secretory proteins in rhesus macaque parotid glands following adenoviral mediated gene transfer. Hum Gene Ther. 2008 ;19(12):1401-5.

39. Samuni Y, Zheng C, Cawley NX, Cotrim AP, Loh YP, Baum BJ. Sorting of growth hormone- erythropoietin fusion proteins in rat salivary glands. Biochem Biophys Res Commun. 2008 Aug 15;373(1):136-9.

40. Cotrim AP, Baum BJ. Gene therapy: some history, applications, problems, and prospects. Toxicol Pathol. 2008;36(1):97-103.

41. Samuni Y, Cawley NX, Zheng C, Cotrim AP, Loh YP, Baum BJ.Sorting behavior of a transgenic erythropoietin-growth hormone fusion protein in murine salivary glands. Hum Gene Ther. 2008 Mar;19(3):279-86.

42. Cotrim AP, Sowers A, Mitchell JB, Baum BJ. Prevention of irradiation-induced salivary hypofunction by microvessel protection in mouse salivary glands. Mol Ther. 2007 Dec;15(12):2101-6. 43. Cotrim AP, Hyodo F, Matsumoto K, Sowers AL, Cook JA, Baum BJ, Krishna MC, Mitchell JB. Differential radiation protection of salivary glands versus tumor by Tempol with accompanying tissue assessment of Tempol by magnetic resonance imaging. Clin Cancer Res. 2007 Aug 15;13(16):4928- 33.

44. Tran SD, Sugito T, Dipasquale G, Cotrim AP, Bandyopadhyay BC, Riddle K, Mooney D, Kok MR, Chiorini JA, Baum BJ. Re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland. Tissue Eng. 2006 Oct;12(10):2939-48. 45. Voutetakis A, Zheng C, Mineshiba F, Cotrim AP, Goldsmith CM, Schmidt M, Afione S, Roescher N, Metzger M, Eckhaus MA, Chiorini JA, Dunbar CE, Donahue RE, Baum BJ. Adeno-associated virus serotype 2-mediated gene transfer to the parotid glands of nonhuman primates. Hum Gene Ther. 2007 Feb;18(2):142-50

46. Lodde BM, Mineshiba F, Kok MR, Wang J, Zheng C, Schmidt M, Cotrim AP, Kriete M, Tak PP, Baum BJ. NOD mouse model for Sjogren's syndrome: lack of longitudinal stability. Oral Dis. 2006 Nov;12(6):566-72

47. Baum BJ, Zheng C, Cotrim AP, Goldsmith CM, Atkinson JC, Brahim JS, Chiorini JA, Voutetakis A, Leakan RA, Van Waes C, Mitchell JB, Delporte C, Wang S, Kaminsky SM, Illei GG. Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunctiion. Biochim Biophys Acta. 2006 Aug;1758(8):1071-7.

48. Cotrim AP, Mineshiba F, Sugito T, Samuni Y, Baum BJ. Salivary gland gene therapy. Dent Clin North Am. 2006 Apr;50(2):157-73.

49. Katano H, Kok MR, Cotrim AP, Yamano S, Schmidt M, Afione S, Baum BJ, Chiorini JA. Enhanced transduction of mouse salivary glands with AAV5-based vectors. Gene Ther. 2006 Apr;13(7):594-601. 50. Wellner RB, Hong S, Cotrim AP, Swaim WD, Baum BJ. Modifying the NH2 and COOH termini of aquaporin-5: effects on localization in polarized epithelial cells. Tissue Eng. 2005 Sep-Oct;11(9- 10):1449-58.

51. Ichijo T, Voutetakis A, Cotrim AP, Bhattachryya N, Fujii M, Chrousos GP, Kino T. The Smad6-histone deacetylase 3 complex silences the transcriptional activity of the glucocorticoid receptor: potential clinical implications. J Biol Chem. 2005 Dec 23;280(51):42067-77. 52. Cotrim AP, Sowers Al, Lodde BM, Vitolo JM, Kingman A, Russo A, Mitchell JB, Baum BJ. Kinetics of Tempol for prevention of xerostomia following head and neck irradiation in a mouse model. Clin Cancer Res. 2005 Oct 15;11(20):7564-8.

53. Muanza TM, Cotrim AP, McAuliffe M, Sowers AL, Baum BJ, Cook JA, Feldchtein F, Amazeen P, Coleman CN, Mitchell JB. Evaluation of radiation-induced oral mucositis by optical coherence tomography. Clin Cancer Res. 2005 Jul 15;11(14):5121-7. 54. Lodde BM, Mineshiba F, Wang J, Cotrim AP, Afione S, Tak PP, Baum BJ. Effect of human vasoactive intestinal peptide gene transfer in a murine model of Sjogren's syndrome. Ann Rheum Dis. 2005 Jun 23

55. Voutetakis A, Bossis I, Kok MR, Zhang W, Wang J, Cotrim AP, Zheng C, Chiorini JA, Nieman LK, Baum BJ. Salivary glands as a potential gene transfer target for gene therapeutics of some monogenetic endocrine disorders. J Endocrinol. 2005 Jun;185(3):363-72. 56. Wellner RB, Cotrim AP, Hong S, Swaim WD, Baum BJ. Localization of AQP5/AQP8 chimeras in MDCK- II cells: Exchange of the N- and C-termini. Biochem Biophys Res Commun. 2005 Apr 29;330(1):172-7.

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57. Kok MR, Voutetakis A, Yamano S, Wang J, Cotrim A, Katano H, Bossis I, Chiorini JA, Tran SD, Tak PP, Baum BJ. Immune responses following salivary gland administration of recombinant adeno- associated virus serotype 2 vectors. J Gene Med. 2005 Apr;7(4):432-41 58. Vitolo JM, Cotrim AP, Sowers AL, Russo A, Wellner R, Pillemer S, Mitchell JB, Baum BJ. The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model. Clin Cancer Res. 2004 Mar 1;10(5):1807-12.

59. Voutetakis A, Kok MR, Zheng C, Bossis I, Wang J, Cotrim AP, Marracino N, Goldsmith CM, Chiorini JA, Loh YP, Nieman LK, Baum BJ. Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics. Proc Natl Acad Sci USA. 2004 Mar 2;101(9):3053-3058. 60. Cotrim P, Martelli-Junior H, Graner E, Sauk JJ, Coletta RD. Cyclosporin A induces proliferation in human gingival fibroblasts via induction of transforming growth factor-beta1. J Periodontol. 2003 Nov;74(11):1625-33.

61. Martelli-Junior H, Cotrim P, Graner E, Sauk JJ, Coletta RD. Effect of transforming growth factor-beta1, interleukin-6, and interferon-gamma on the expression of type I collagen, heat shock protein 47, matrix metalloproteinase (MMP)-1 and MMP-2 by fibroblasts from normal gingiva and hereditary gingival fibromatosis. J Periodontol. 2003 Mar;74(3):296-306. 62. Cotrim P, Andrade CR, Martelli-Junior H, Graner E, Sauk JJ, Coletta RD, Expression of Matrix Metalloproteinases in Cyclosporin-treated Gingival fibroblast is regulated by transforming growth factor

(TGF) – β1 autocrine stimulation. J Periodontol 2002 Nov;73(11):1313-22. 63. Cotrim P, Andrade C, Line SR., Coletta RD.,Expression and activity of matrix metalloproteinase-2

(MMP-2) in the development of rat molar tooth germ. Braz Dent J. 2002; 13(2):97-102 64. Coletta RD, Cotrim P, Almeida OP, Alves VA, Wakamatsu A, Vargas PA. Basaloid squamous carcinoma of oral cavity: a histologic and immunohistochemical study. Oral Oncol. 2002 Oct;38(7):723-9. 65. Coletta RD., Cotrim P, Vargas PA., Villalba H, Pires FR., Moraes M, Almeida OP., Basaloid squamous carcinoma of the oral cavity: Report of 2 cases and study of AgNOR, PCNA, p53, and MMP expression. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:563-9. 66. de Andrade CR, Cotrin P, Graner E, Almeida OP, Sauk JJ, Coletta JJ. – TGF-beta1 autocrine stimulation regulates fibroblast proliferation in hereditary gingival fibromatosis. Journal Periodontol. 2001 Dec; 72(12):1726-33

67. Cotrim P, Fregnani E., Villalba H, Vargas P, Almeida O, Coletta RD. Oral squamous cell carcinoma: Review. Brazilian Journal of Surgery and Implant – Editora Maio – May, 2001.

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