Nadia Roan, PhD

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Nadia Roan, PhD

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Senior Investigator, Gladstone Institutes
Professor, School of Medicine
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Biography

Dr. Roan has had a long-standing interest in understanding the effect of host factors on microbial pathogens of the genital mucosa. Her research as a graduate student led to new insights into the nature of the mucosal immune response directed against the most common sexually transmitted bacterium C. trachomatis. She created and characterized C. trachomatis-specific TCR transgenic and retrogenic mice, and used these mice as tools to understand the inflammatory response to C. trachomatis within the upper female reproductive tract (FRT). During her postdoctoral years, Dr. Roan continued her studies on sexually transmitted microbes, but transitioned to studying HIV-1, a viral pathogen with a devastating effect on global health. She focused on understanding the effect of semen components on HIV-1 infection. She identified and characterized amyloid fibrils made up of peptides derived from the major components of the semen coagulum. These amyloids markedly enhance HIV infection, in part by promoting the attachment of HIV-1 to their cellular targets.

Dr. Roan’s current research interest focuses on two major areas. First, she is investigating the mechanisms by which semen components such as coagulum-derived amyloids promote HIV transmission, and the effects of these components on the effectiveness of currently available anti-HIV microbicides. This understanding will help the development of a new class of “combination microbicides” that contain components targeting both HIV-1 and naturally-occurring factors that promote HIV-1 infectivity. In parallel, a high-throughput screen is currently being conducted to identify compounds that inhibit the activity of viral-enhancing factors in semen. Dr. Roan’s second line of research is to understand the physiological functions of semen amyloids and their effects on cells present in the genital mucosa. This understanding will reveal insights into the roles of these semen factors in reproduction, which can lead to novel ways to enhance fertility or to the development of a new class of contraceptives.

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  1. Thomas Alexander Packard, Xiaoyu Luo, Zachary W. Grimmett, Eytan Herzig, Nadia R. Roan, Warner C. Greene. Establishing the HIV reservoir: HIV-susceptible cells and the signals that recruit them. The Journal of Immunology. 2018 May 1; 200(1_Supplement):182.4-182.4.
  2. Trapecar M, Khan S, Roan NR, Chen TH, Telwatte S, Deswal M, Pao M, Somsouk M, Deeks SG, Hunt PW, Yukl S, Sanjabi S. An Optimized and Validated Method for Isolation and Characterization of Lymphocytes from HIV+ Human Gut Biopsies. AIDS Res Hum Retroviruses. 2017 Nov; 33(S1):S31-S39.
  3. Cavrois M, Banerjee T, Mukherjee G, Raman N, Hussien R, Rodriguez BA, Vasquez J, Spitzer MH, Lazarus NH, Jones JJ, Ochsenbauer C, McCune JM, Butcher EC, Arvin AM, Sen N, Greene WC, Roan NR. Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+ T Cells. Cell Rep. 2017 07 25; 20(4):984-998.
  4. Roan NR, Sandi-Monroy N, Kohgadai N, Usmani SM, Hamil KG, Neidleman J, Montano M, Ständker L, Röcker A, Cavrois M, Rosen J, Marson K, Smith JF, Pilcher CD, Gagsteiger F, Sakk O, O'Rand M, Lishko PV, Kirchhoff F, Münch J, Greene WC. Semen amyloids participate in spermatozoa selection and clearance. Elife. 2017 06 27; 6.
  5. Thomas Alexander Packard, Eytan Herzig, Nadia R Roan, Warner C Greene. Establishing the HIV reservoir: HIV-susceptible cells and the signals that recruit them. The Journal of Immunology. 2017 May 1; 198(1_Supplement):125.1-125.1.
  6. Neidleman JA, Chen JC, Kohgadai N, Müller JA, Laustsen A, Thavachelvam K, Jang KS, Stürzel CM, Jones JJ, Ochsenbauer C, Chitre A, Somsouk M, Garcia MM, Smith JF, Greenblatt RM, Münch J, Jakobsen MR, Giudice LC, Greene WC, Roan NR. Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells. PLoS Pathog. 2017 02; 13(2):e1006163.
  7. Camus C, Matusali G, Bourry O, Mahe D, Aubry F, Bujan L, Pasquier C, Massip P, Ravel C, Zirafi O, Munch J, Roan NR, Pineau C, Dejucq-Rainsford N. Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection. AIDS. 2016 05 15; 30(8):1197-208.
  8. LoRicco JG, Xu CS, Neidleman J, Bergkvist M, Greene WC, Roan NR, Makhatadze GI. Gallic Acid Is an Antagonist of Semen Amyloid Fibrils That Enhance HIV-1 Infection. J Biol Chem. 2016 Jul 01; 291(27):14045-14055.
  9. Bergman P, Roan NR, Römling U, Bevins CL, Münch J. Amyloid formation: functional friend or fearful foe? J Intern Med. 2016 Aug; 280(2):139-52.
  10. Müller JA, Zirafi O, Roan NR, Lee SJ, Münch J. Evaluation of EPI-X4 as a urinary peptide biomarker for diagnosis and prognosis of late acute GvHD. Bone Marrow Transplant. 2016 08; 51(8):1137-9.
  11. Roan NR, Jakobsen MR. Friend or Foe: Innate Sensing of HIV in the Female Reproductive Tract. Curr HIV/AIDS Rep. 2016 Feb; 13(1):53-63.
  12. Chen JC, Roan NR. Isolation and Culture of Human Endometrial Epithelial Cells and Stromal Fibroblasts. Bio Protoc. 2015 Oct 20; 5(20).
  13. Roan NR, Münch J. Improving preclinical models of HIV microbicide efficacy. Trends Microbiol. 2015 Aug; 23(8):445-7.
  14. Zirafi O, Kim KA, Roan NR, Kluge SF, Müller JA, Jiang S, Mayer B, Greene WC, Kirchhoff F, Münch J. Semen enhances HIV infectivity and impairs the antiviral efficacy of microbicides. Sci Transl Med. 2014 Nov 12; 6(262):262ra157.
  15. French KC, Roan NR, Makhatadze GI. Structural characterization of semen coagulum-derived SEM1(86-107) amyloid fibrils that enhance HIV-1 infection. Biochemistry. 2014 May 27; 53(20):3267-77.
  16. Roan NR, Liu H, Usmani SM, Neidleman J, Müller JA, Avila-Herrera A, Gawanbacht A, Zirafi O, Chu S, Dong M, Kumar ST, Smith JF, Pollard KS, Fändrich M, Kirchhoff F, Münch J, Witkowska HE, Greene WC. Liquefaction of semen generates and later degrades a conserved semenogelin peptide that enhances HIV infection. J Virol. 2014 Jul; 88(13):7221-34.
  17. Roan NR, Chu S, Liu H, Neidleman J, Witkowska HE, Greene WC. Interaction of fibronectin with semen amyloids synergistically enhances HIV infection. J Infect Dis. 2014 Oct 01; 210(7):1062-6.
  18. Usmani SM, Zirafi O, Müller JA, Sandi-Monroy NL, Yadav JK, Meier C, Weil T, Roan NR, Greene WC, Walther P, Nilsson KP, Hammarström P, Wetzel R, Pilcher CD, Gagsteiger F, Fändrich M, Kirchhoff F, Münch J. Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen. Nat Commun. 2014 Apr 01; 5:3508.
  19. Chen JC, Johnson BA, Erikson DW, Piltonen TT, Barragan F, Chu S, Kohgadai N, Irwin JC, Greene WC, Giudice LC, Roan NR. Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts. Hum Reprod. 2014 Jun; 29(6):1255-70.
  20. Tang Q, Roan NR, Yamamura Y. Seminal plasma and semen amyloids enhance cytomegalovirus infection in cell culture. J Virol. 2013 Dec; 87(23):12583-91.
  21. Yolamanova M, Meier C, Shaytan AK, Vas V, Bertoncini CW, Arnold F, Zirafi O, Usmani SM, Müller JA, Sauter D, Goffinet C, Palesch D, Walther P, Roan NR, Geiger H, Lunov O, Simmet T, Bohne J, Schrezenmeier H, Schwarz K, Ständker L, Forssmann WG, Salvatella X, Khalatur PG, Khokhlov AR, Knowles TP, Weil T, Kirchhoff F, Münch J. Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses. Nat Nanotechnol. 2013 Feb; 8(2):130-6.
  22. Roan NR, Cavrois M, Greene WC. [Role of semen-derived amyloid fibrils as facilitators of HIV infection]. Med Sci (Paris). 2012 Apr; 28(4):358-60.
  23. Roan NR, Müller JA, Liu H, Chu S, Arnold F, Stürzel CM, Walther P, Dong M, Witkowska HE, Kirchhoff F, Münch J, Greene WC. Peptides released by physiological cleavage of semen coagulum proteins form amyloids that enhance HIV infection. . 2011 Dec 15; 10(6):541-50.
  24. Arnold F, Schnell J, Zirafi O, Stürzel C, Meier C, Weil T, Ständker L, Forssmann WG, Roan NR, Greene WC, Kirchhoff F, Münch J. Naturally occurring fragments from two distinct regions of the prostatic acid phosphatase form amyloidogenic enhancers of HIV infection. J Virol. 2012 Jan; 86(2):1244-9.
  25. Kim KA, Yolamanova M, Zirafi O, Roan NR, Staendker L, Forssmann WG, Burgener A, Dejucq-Rainsford N, Hahn BH, Shaw GM, Greene WC, Kirchhoff F, Münch J. Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. Retrovirology. 2010 Jun 23; 7:55.