nadia.roan@gladstone.ucsf.edu

Nadia Roan investigates the transmission of the HIV/AIDS virus across the human genital tract. Using a variety of cell-based assays, she is uncovering how various mucosal components present in the female reproductive tract can facilitate or hinder infection by HIV. Her lab is also probing the features of T cells, HIV’s normal targets, that make these cells susceptible to productive versus latent HIV infection, and studying how HIV is able to “hide” in reservoir cells in individuals taking antiretroviral therapy. Her work has implications for stemming heterosexual HIV transmission, which accounts for most new HIV infections worldwide, and for developing cures against HIV/AIDS.

Disease Areas

HIV/AIDS

Infertility

Sexually Transmitted Pathogens

Women’s Health

Zika Virus

Areas of Expertise

Host-Pathogen Interactions

Multiparameter Single-Cell Phenotyping (CyTOF and Flow Cytometry)

Mucosal Immunology

Reproductive Health

Single-cell RNAseq Analysis, Antibody-seq

T Cell Biology

Lab Focus

Understanding how factors in semen and various cell types of the genital mucosa differentially impact HIV’s ability to infect target T cells.

Using high-dimensional single-cell phenotyping (e.g. CyTOF) to understand the molecular basis of differential susceptibility of T cells to HIV infection, and how HIV is able to persist in individuals on antiretroviral therapy

Characterizing how soluble factors in semen signal to the female reproductive tract to promote fertility.

Research Impact

Roan’s lab has demonstrated that cells lining the mucosal surface of the rectum and female genital tract secrete antiviral factors, whereas cells deeper in the mucosa potentiate HIV’s ability to infect T cells. These observations suggest that abrasions to the mucosal surface during intercourse allow HIV’s spread by facilitating its access to an environment favoring infection. The lab is now characterizing the molecular mechanisms by which genital cells prevent or potentiate HIV’s infectivity in the mucosa, which may lead to new protective strategies against HIV transmission.

Roan’s lab has also successfully applied CyTOF with a panel of 38 phenotypic markers to characterize the types of T cells targeted by HIV. Their work is uncovering the types of cells most and least susceptible to infection, identifying molecules whose expression is modified upon HIV infection, and finding markers of cells that preferentially undergo productive versus latent infection, which has important implications for the eventual eradication of latent virus in infected individuals.

Professional Titles

Associate Investigator, Gladstone Institutes

Associate Professor of Urology, UC San Francisco

Bio

Nadia Roan is an associate investigator at Gladstone Institutes and an associate professor of urology at UC San Francisco (UCSF).

She received her undergraduate training from UC Berkeley, and completed her PhD in the biological and biomedical sciences program at Harvard Medical School studying T cell responses to the bacterium Chlamydia trachomatis. She conducted her postdoctoral studies at Gladstone Institutes, where she studied the mechanisms by which host factors in human semen influence HIV infection. As a staff scientist at Gladstone, she further identified and characterized novel factors from semen that influence infection outcome. Since starting her own lab in the department of urology at UCSF, she has continued to study the relationship between semen factors and HIV transmission, and pursued research to more broadly understand the molecular basis by which HIV establishes infection in mucosal tissues.

The current focus of her lab is to use single-cell analytical approaches including CyTOF to characterize the molecular basis of cellular susceptibility to HIV infection and pathogenesis, and to identify signatures of infectious and reproductive diseases in humans.

How Did You Get Your Start in Science?

After I finished my college freshman year, I joined a lab where I got introduced to the whole concept of experimental research, and got hooked from there on!

Nadia Roan, PhD

Honors and Awards

2013 Hellman Award for Early-Career Faculty

2013 K99 Pathway to Independence Award

2012 Gladstone Institute of Virology and Immunology Award for Scientific Excellence

2012 Centers for AIDS Research Early Career Award of Excellence in Basic Research

Publications

Shared Mechanisms Govern HIV Transcriptional Suppression in Circulating CD103+ and Gut CD4+ T Cells. Yukl SA, Khan S, Chen TH, Trapecar M, Wu F, Xie G, Telwatte S, Fulop D, Pico AR, Laird GM, Ritter KD, Jones NG, Lu CM, Siliciano RF, Roan NR, Milush JM, Somsouk M, Deeks SG, Hunt PW, Sanjabi S. J Virol. 2020 Oct 28.
The HIV-1 latent reservoir is largely sensitive to circulating T cells. Warren JA, Zhou S, Xu Y, Moeser MJ, MacMillan DR, Council O, Kirchherr J, Sung JM, Roan N, Adimora AA, Joseph S, Kuruc JD, Gay CL, Margolis DM, Archin N, Brumme ZL, Swanstrom R, Goonetilleke N. Elife. 2020 Oct 06; 9.
Phenotypic analysis of the unstimulated in vivo HIV CD4 T cell reservoir. Neidleman J, Luo X, Frouard J, Xie G, Hsiao F, Ma T, Morcilla V, Lee A, Telwatte S, Thomas R, Tamaki W, Wheeler B, Hoh R, Somsouk M, Vohra P, Milush J, James KS, Archin NM, Hunt PW, Deeks SG, Yukl SA, Palmer S, Greene WC, Roan NR. Elife. 2020 Sep 29; 9.
Reproductive tract immune cells from pregnant women or those using depot medroxyprogesterone acetate show no excess susceptibility to HIV-1: results of an ex vivo fusion assay. Seidman D, Cavrois M, Hilton JF, Roan NR, Averbach S, Takeda M, Chang E, Raman N, Greenblatt R, Shacklett BL, Smith-McCune K. Contraception. 2020 Sep 29.
Sequence-independent recognition of the amyloid structural motif by GFP protein family. Xu SCS, LoRicco JG, Bishop AC, James NA, Huynh WH, McCallum SA, Roan NR, Makhatadze GI. Proc Natl Acad Sci U S A. 2020 09 08; 117(36):22122-22127.
SARS-CoV-2-Specific T Cells Exhibit Phenotypic Features of Helper Function, Lack of Terminal Differentiation, and High Proliferation Potential. Neidleman J, Luo X, Frouard J, Xie G, Gill G, Stein ES, McGregor M, Ma T, George AF, Kosters A, Greene WC, Vasquez J, Ghosn E, Lee S, Roan NR. Cell Rep Med. 2020 Sep 22; 1(6):100081.
Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy. Colomb F, Giron LB, Kuri-Cervantes L, Adeniji OS, Ma T, Dweep H, Battivelli E, Verdin E, Palmer CS, Tateno H, Kossenkov AV, Roan NR, Betts MR, Abdel-Mohsen M. Cell Rep. 2020 Aug 04; 32(5):107991.
Seminal Plasma-Derived Extracellular-Vesicle Fractions from HIV-Infected Men Exhibit Unique MicroRNA Signatures and Induce a Proinflammatory Response in Cells Isolated from the Female Reproductive Tract. Marques de Menezes EG, Jang K, George AF, Nyegaard M, Neidleman J, Inglis HC, Danesh A, Deng X, Afshari A, Kim YH, Billaud JN, Marson K, Pilcher CD, Pillai SK, Norris PJ, Roan NR. J Virol. 2020 Jul 30; 94(16).
Loss of Preexisting Immunological Memory Among Human Immunodeficiency Virus-Infected Women Despite Immune Reconstitution With Antiretroviral Therapy. Thomas A, Hammarlund E, Gao L, Holman S, Michel KG, Glesby M, Villacres MC, Golub ET, Roan NR, French AL, Augenbraun MH, Slifka MK. J Infect Dis. 2020 Jun 29; 222(2):243-251.
Impact of biological sex on immune activation and frequency of the latent HIV reservoir during suppressive antiretroviral therapy. Falcinelli SD, Shook-Sa BE, Dewey MG, Sridhar S, Read J, Kirchherr J, James KS, Allard B, Ghofrani S, Stuelke E, Baker C, Roan NR, Eron JJ, Kuruc JD, Ramirez C, Gay C, Mollan KR, Margolis DM, Adimora AA, Archin NM. J Infect Dis. 2020 Jun 04.
HIV efficiently infects T cells from the endometrium and remodels them to promote systemic viral spread. Ma T, Luo X, George AF, Mukherjee G, Sen N, Spitzer TL, Giudice LC, Greene WC, Roan NR. Elife. 2020 May 26; 9.
Tissue memory CD4+ T cells expressing IL-7 receptor-alpha (CD127) preferentially support latent HIV-1 infection. Hsiao F, Frouard J, Gramatica A, Xie G, Telwatte S, Lee GQ, Roychoudhury P, Schwarzer R, Luo X, Yukl SA, Lee S, Hoh R, Deeks SG, Jones RB, Cavrois M, Greene WC, Roan NR. PLoS Pathog. 2020 04; 16(4):e1008450.
Seminal plasma promotes decidualization of endometrial stromal fibroblasts in vitro from women with and without inflammatory disorders in a manner dependent on interleukin-11 signaling. George AF, Jang KS, Nyegaard M, Neidleman J, Spitzer TL, Xie G, Chen JC, Herzig E, Laustsen A, Marques de Menezes EG, Houshdaran S, Pilcher CD, Norris PJ, Jakobsen MR, Greene WC, Giudice LC, Roan NR. Hum Reprod. 2020 03 27; 35(3):617-640.
Measuring the contribution of γδ T cells to the persistent HIV reservoir. James KS, Trumble I, Clohosey ML, Moeser M, Roan NR, Adimora AA, Joseph SB, Archin NM, Hudgens M, Soriano-Sarabia N. AIDS. 2020 03 01; 34(3):363-371.
Effects of the levonorgestrel-containing intrauterine device, copper intrauterine device, and levonorgestrel-containing oral contraceptive on susceptibility of immune cells from cervix, endometrium and blood to HIV-1 fusion measured ex vivo. Cavrois M, Hilton JF, Roan NR, Takeda M, Seidman D, Averbach S, Chang E, Raman N, Greenblatt R, Shacklett BL, Smith-McCune K. PLoS One. 2019; 14(8):e0221181.
Single-cell Motility Analysis of Tethered Human Spermatozoa. Skinner WM, Mannowetz N, Lishko PV, Roan NR. Bio Protoc. 2019 Mar 05; 9(5).
Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function. Laustsen A, Bak RO, Krapp C, Kjær L, Egedahl JH, Petersen CC, Pillai S, Tang HQ, Uldbjerg N, Porteus M, Roan NR, Nyegaard M, Denton PW, Jakobsen MR. Nat Commun. 2018 08 30; 9(1):3525.
Potent and rapid activation of tropomyosin-receptor kinase A in endometrial stromal fibroblasts by seminal plasma. Martin JW, Chen JC, Neidleman J, Tatsumi K, Hu J, Giudice LC, Greene WC, Roan NR. Biol Reprod. 2018 08 01; 99(2):336-348.
Structure, function and antagonism of semen amyloids. Röcker A, Roan NR, Yadav JK, Fändrich M, Münch J. Chem Commun (Camb). 2018 Jul 05; 54(55):7557-7569.
Semen inhibits Zika virus infection of cells and tissues from the anogenital region. Müller JA, Harms M, Krüger F, Groß R, Joas S, Hayn M, Dietz AN, Lippold S, von Einem J, Schubert A, Michel M, Mayer B, Cortese M, Jang KS, Sandi-Monroy N, Deniz M, Ebner F, Vapalahti O, Otto M, Bartenschlager R, Herbeuval JP, Schmidt-Chanasit J, Roan NR, Münch J. Nat Commun. 2018 06 07; 9(1):2207.
Resident T cells stand up to HIV. Roan NR. Sci Immunol. 2018 06 01; 3(24).
An Optimized and Validated Method for Isolation and Characterization of Lymphocytes from HIV+ Human Gut Biopsies. Trapecar M, Khan S, Roan NR, Chen TH, Telwatte S, Deswal M, Pao M, Somsouk M, Deeks SG, Hunt PW, Yukl S, Sanjabi S. AIDS Res Hum Retroviruses. 2017 Nov; 33(S1):S31-S39.
Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+ T Cells. 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. Cell Rep. 2017 07 25; 20(4):984-998.
Semen amyloids participate in spermatozoa selection and clearance. 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. Elife. 2017 06 27; 6.
Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells. 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. PLoS Pathog. 2017 02; 13(2):e1006163.
Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection. 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. AIDS. 2016 05 15; 30(8):1197-208.
Gallic Acid Is an Antagonist of Semen Amyloid Fibrils That Enhance HIV-1 Infection. LoRicco JG, Xu CS, Neidleman J, Bergkvist M, Greene WC, Roan NR, Makhatadze GI. J Biol Chem. 2016 Jul 01; 291(27):14045-55.
Amyloid formation: functional friend or fearful foe? Bergman P, Roan NR, Römling U, Bevins CL, Münch J. J Intern Med. 2016 Aug; 280(2):139-52.
Evaluation of EPI-X4 as a urinary peptide biomarker for diagnosis and prognosis of late acute GvHD. Müller JA, Zirafi O, Roan NR, Lee SJ, Münch J. Bone Marrow Transplant. 2016 08; 51(8):1137-9.
Friend or Foe: Innate Sensing of HIV in the Female Reproductive Tract. Roan NR, Jakobsen MR. Curr HIV/AIDS Rep. 2016 Feb; 13(1):53-63.
Isolation and Culture of Human Endometrial Epithelial Cells and Stromal Fibroblasts. Chen JC, Roan NR. Bio Protoc. 2015 Oct 20; 5(20).
Improving preclinical models of HIV microbicide efficacy. Roan NR, Münch J. Trends Microbiol. 2015 Aug; 23(8):445-7.
Semen enhances HIV infectivity and impairs the antiviral efficacy of microbicides. Zirafi O, Kim KA, Roan NR, Kluge SF, Müller JA, Jiang S, Mayer B, Greene WC, Kirchhoff F, Münch J. Sci Transl Med. 2014 Nov 12; 6(262):262ra157.
HIV-enhancing Amyloids Are Prevalent in Fresh Semen and Are a Determinant for Semen's Ability to Enhance HIV Infection: Relevance for HIV Transmission. Shariq Usmani, Haichuan Liu, Chris D. Pilcher, H. Ewa Witkowska, Frank Kirchhoff, Warner C. Greene, Jan Münch, Nadia R. Roan. AIDS Research and Human Retroviruses. 2014 Oct 1; 30(S1):a183-a184.
Semen-mediated Enhancement of HIV Infection Markedly Impairs the Antiviral Efficacy of Microbicides. Onofrio Zirafi, Kyeong-Ae Kim, Nadia R. Roan, Benjamin Mayer, Silvia Kluge, Shibo Jiang, Warner C. Greene, Frank Kirchhoff, Jan Münch. AIDS Research and Human Retroviruses. 2014 Oct 1; 30(S1):a183-a183.
Structural characterization of semen coagulum-derived SEM1(86-107) amyloid fibrils that enhance HIV-1 infection. French KC, Roan NR, Makhatadze GI. Biochemistry. 2014 May 27; 53(20):3267-77.
Liquefaction of semen generates and later degrades a conserved semenogelin peptide that enhances HIV infection. 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. J Virol. 2014 Jul; 88(13):7221-34.
Interaction of fibronectin with semen amyloids synergistically enhances HIV infection. Roan NR, Chu S, Liu H, Neidleman J, Witkowska HE, Greene WC. J Infect Dis. 2014 Oct 01; 210(7):1062-6.
Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen. 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. Nat Commun. 2014 Apr 01; 5:3508.
Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts. Chen JC, Johnson BA, Erikson DW, Piltonen TT, Barragan F, Chu S, Kohgadai N, Irwin JC, Greene WC, Giudice LC, Roan NR. Hum Reprod. 2014 Jun; 29(6):1255-70.
Seminal plasma and semen amyloids enhance cytomegalovirus infection in cell culture. Tang Q, Roan NR, Yamamura Y. J Virol. 2013 Dec; 87(23):12583-91.
Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses. 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. Nat Nanotechnol. 2013 Feb; 8(2):130-6.
Pro-inflammatory effects of seminal plasma on human endometrium: implications for implantation and human immunodeficiency virus (HIV) transmission. B.A. Johnson, J. Chen, N. Roan, F. Barragan, J. Irwin, L.C. Giudice. Fertility and Sterility. 2012 Sep 1; 98(3):s221.
[Role of semen-derived amyloid fibrils as facilitators of HIV infection]. Roan NR, Cavrois M, Greene WC. Med Sci (Paris). 2012 Apr; 28(4):358-60.
Peptides released by physiological cleavage of semen coagulum proteins form amyloids that enhance HIV infection. Roan NR, Müller JA, Liu H, Chu S, Arnold F, Stürzel CM, Walther P, Dong M, Witkowska HE, Kirchhoff F, Münch J, Greene WC. . 2011 Dec 15; 10(6):541-50.
Naturally occurring fragments from two distinct regions of the prostatic acid phosphatase form amyloidogenic enhancers of HIV infection. Arnold F, Schnell J, Zirafi O, Stürzel C, Meier C, Weil T, Ständker L, Forssmann WG, Roan NR, Greene WC, Kirchhoff F, Münch J. J Virol. 2012 Jan; 86(2):1244-9.
Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. 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. Retrovirology. 2010 Jun 23; 7:55.
Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer of viral infection). Roan NR, Sowinski S, Münch J, Kirchhoff F, Greene WC. J Biol Chem. 2010 Jan 15; 285(3):1861-9.
T cell responses in the absence of IFN-gamma exacerbate uterine infection with Chlamydia trachomatis. Gondek DC, Roan NR, Starnbach MN. J Immunol. 2009 Jul 15; 183(2):1313-9.
The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection. Roan NR, Münch J, Arhel N, Mothes W, Neidleman J, Kobayashi A, Smith-McCune K, Kirchhoff F, Greene WC. J Virol. 2009 Jan; 83(1):73-80.
Conquering sexually transmitted diseases. Starnbach MN, Roan NR. Nat Rev Immunol. 2008 Apr; 8(4):313-7.
Discovery of CD8+ T cell epitopes in Chlamydia trachomatis infection through use of caged class I MHC tetramers. Grotenbreg GM, Roan NR, Guillen E, Meijers R, Wang JH, Bell GW, Starnbach MN, Ploegh HL. Proc Natl Acad Sci U S A. 2008 Mar 11; 105(10):3831-6.
A seminal finding for understanding HIV transmission. Roan NR, Greene WC. Cell. 2007 Dec 14; 131(6):1044-6.
Immune-mediated control of Chlamydia infection. Roan NR, Starnbach MN. Cell Microbiol. 2008 Jan; 10(1):9-19.
Antigen-specific CD8+ T cells respond to Chlamydia trachomatis in the genital mucosa. Roan NR, Starnbach MN. J Immunol. 2006 Dec 01; 177(11):7974-9.
Monitoring the T cell response to genital tract infection. Roan NR, Gierahn TM, Higgins DE, Starnbach MN. Proc Natl Acad Sci U S A. 2006 Aug 08; 103(32):12069-74.
Developmental regulation of Chlamydia trachomatis class I accessible protein-1, a CD8+ T cell antigen. Balsara ZR, Roan NR, Steele LN, Starnbach MN. J Infect Dis. 2006 May 15; 193(10):1459-63.
Spt10-dependent transcriptional activation in Saccharomyces cerevisiae requires both the Spt10 acetyltransferase domain and Spt21. Hess D, Liu B, Roan NR, Sternglanz R, Winston F. Mol Cell Biol. 2004 Jan; 24(1):135-43.
The Listeria monocytogenes lemA gene product is not required for intracellular infection or to activate fMIGWII-specific T cells. D'Orazio SE, Velasquez M, Roan NR, Naveiras-Torres O, Starnbach MN. Infect Immun. 2003 Dec; 71(12):6721-7.

More Publications

Contact

Nadia Roan

415.734.4883

Robin Givens
Senior Executive Assistant
415.734.4805

Roan Lab Website

Lab Members

Julie Frouard, PhD

Postdoctoral Scholar

Ashley George, PhD

Postdoctoral Scholar

Matthew McGregor

Research Associate I

Jason Neidleman

Senior Research Associate