Nadia Roan, PhD

Professor in Residence
Urology
+1 415 734-4883

The Roan Lab studies how intracellular and extracellular factors in the tissue microenvironment can affect infection by HIV, mucosal immunity, and reproductive health. We have demonstrated that genital and rectal fibroblasts, amongst the most abundant cells of the mucosa, potently increase HIV infection of T cells through at least two distinct mechanisms: promoting viral entry, and altering the cellular state of T cells to render them more permissive to viral replication. To characterize the molecular basis of how intrinsic and extrinsic perturbations can render some subsets of CD4+ T cells more susceptible than others to HIV infection, we are using a variety of global gene expression analysis approaches, including CyTOF and RNA-seq. These approaches are also being used to characterize the HIV latent reservoir and the nature of viral rebound upon antiretroviral treatment interruption. Another research interest in the lab is to understand how factors in seminal plasma affect reproductive health and susceptibility to sexually transmitted diseases.

Publications: 

CCL2: a Chemokine Potentially Promoting Early Seeding of the Latent HIV Reservoir.

mBio

Packard TA, Schwarzer R, Herzig E, Rao D, Luo X, Egedal JH, Hsiao F, Widera M, Hultquist JF, Grimmett ZW, Messer RJ, Krogan NJ, Deeks SG, Roan NR, Dittmer U, Hasenkrug KJ, Greene WC

SARS-CoV-2 Delta variant induces enhanced pathology and inflammatory responses in K18-hACE2 mice.

PloS one

Lee KS, Wong TY, Russ BP, Horspool AM, Miller OA, Rader NA, Givi JP, Winters MT, Wong ZYA, Cyphert HA, Denvir J, Stoilov P, Barbier M, Roan NR, Amin MS, Martinez I, Bevere JR, Damron FH

Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV.

Viruses

George AF, McGregor M, Gingrich D, Neidleman J, Marquez RS, Young KC, Thanigaivelan KL, Greene WC, Tien PC, Deitchman AN, Spitzer TL, Roan NR

Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq.

Frontiers in immunology

Luo X, Frouard J, Zhang G, Neidleman J, Xie G, Sheedy E, Roan NR, Greene WC

Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination.

Nature

Suryawanshi RK, Chen IP, Ma T, Syed AM, Brazer N, Saldhi P, Simoneau CR, Ciling A, Khalid MM, Sreekumar B, Chen PY, Kumar GR, Montano M, Gascon R, Tsou CL, Garcia-Knight MA, Sotomayor-Gonzalez A, Servellita V, Gliwa A, Nguyen J, Silva I, Milbes B, Kojima N, Hess V, Shacreaw M, Lopez L, Brobeck M, Turner F, Soveg FW, George AF, Fang X, Maishan M, Matthay M, Morris MK, Wadford D, Hanson C, Greene WC, Andino R, Spraggon L, Roan NR, Chiu CY, Doudna JA, Ott M

Deep immunophenotyping reveals endometriosis is marked by dysregulation of the mononuclear phagocytic system in endometrium and peripheral blood.

BMC medicine

Vallvé-Juanico J, George AF, Sen S, Thomas R, Shin MG, Kushnoor D, Vásquez JJ, Vo KC, Irwin JC, Roan NR, Combes AJ, Giudice LC

Common and Divergent Features of T Cells from Blood, Gut, and Genital Tract of Antiretroviral Therapy-Treated HIV+ Women.

Journal of immunology (Baltimore, Md. : 1950)

Xie G, Moron-Lopez S, Siegel DA, Yin K, Polos A, Cohen J, Greenblatt RM, Tien PC, Lee SA, Yukl SA, Roan NR

T-cell immune dysregulation and mortality in women with HIV.

The Journal of infectious diseases

Peters BA, Moon JY, Hanna DB, Kutsch O, Fischl M, Moran CA, Adimora AA, Gange S, Roan NR, Michel KG, Augenbraun M, Sharma A, Landay A, Desai S, Kaplan RC

Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals.

Frontiers in immunology

George AF, Luo X, Neidleman J, Hoh R, Vohra P, Thomas R, Shin MG, Lee MJ, Blish CA, Deeks SG, Greene WC, Lee SA, Roan NR

Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C-C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status.

Frontiers in microbiology

Pedersen JG, Egedal JH, Packard TA, Thavachelvam K, Xie G, van der Sluis RM, Greene WC, Roan NR, Jakobsen MR

Siglec-9 defines and restrains a natural killer subpopulation highly cytotoxic to HIV-infected cells.

PLoS pathogens

Adeniji OS, Kuri-Cervantes L, Yu C, Xu Z, Ho M, Chew GM, Shikuma C, Tomescu C, George AF, Roan NR, Ndhlovu LC, Liu Q, Muthumani K, Weiner DB, Betts MR, Xiao H, Abdel-Mohsen M

Protracted yet Coordinated Differentiation of Long-Lived SARS-CoV-2-Specific CD8+ T Cells during Convalescence.

Journal of immunology (Baltimore, Md. : 1950)

Ma T, Ryu H, McGregor M, Babcock B, Neidleman J, Xie G, George AF, Frouard J, Murray V, Gill G, Ghosn E, Newell EW, Lee SA, Roan NR

Tissue-specific differences in HIV DNA levels and mechanisms that govern HIV transcription in blood, gut, genital tract and liver in ART-treated women.

Journal of the International AIDS Society

Moron-Lopez S, Xie G, Kim P, Siegel DA, Lee S, Wong JK, Price JC, Elnachef N, Greenblatt RM, Tien PC, Roan NR, Yukl SA

Reliable Estimation of CD8 T Cell Inhibition of In Vitro HIV-1 Replication.

Frontiers in immunology

Xu Y, Weideman AM, Abad-Fernandez M, Mollan KR, Kallon S, Samir S, Warren JA, Clutton G, Roan N, Adimora AA, Archin N, Kuruc J, Gay C, Hudgens MG, Goonetilleke N

Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19.

Cell reports

Neidleman J, Luo X, George AF, McGregor M, Yang J, Yun C, Murray V, Gill G, Greene WC, Vasquez J, Lee SA, Ghosn E, Lynch KL, Roan NR

Hyaluronic acid is a negative regulator of mucosal fibroblast-mediated enhancement of HIV infection.

Mucosal immunology

Egedal JH, Xie G, Packard TA, Laustsen A, Neidleman J, Georgiou K, Pillai SK, Greene WC, Jakobsen MR, Roan NR

Characterization of HIV-induced remodeling reveals differences in infection susceptibility of memory CD4+ T cell subsets in vivo.

Cell reports

Xie G, Luo X, Ma T, Frouard J, Neidleman J, Hoh R, Deeks SG, Greene WC, Roan NR

Evaluating a New Class of AKT/mTOR Activators for HIV Latency Reversing Activity Ex Vivo and In Vivo.

Journal of virology

Gramatica A, Schwarzer R, Brantley W, Varco-Merth B, Sperber HS, Hull PA, Montano M, Migueles SA, Rosenthal D, Hogan LE, Johnson JR, Packard TA, Grimmett ZW, Herzig E, Besnard E, Nekorchuk M, Hsiao F, Deeks SG, Snape M, Kiernan B, Roan NR, Lifson JD, Estes JD, Picker LJ, Verdin E, Krogan NJ, Henrich TJ, Connors M, Ott M, Pillai SK, Okoye AA, Greene WC

Shared Mechanisms Govern HIV Transcriptional Suppression in Circulating CD103+ and Gut CD4+ T Cells.

Journal of virology

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

Impact of biological sex on immune activation and frequency of the latent HIV reservoir during suppressive antiretroviral therapy.

The Journal of infectious diseases

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

The HIV-1 latent reservoir is largely sensitive to circulating T cells.

eLife

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

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.

Contraception

Seidman D, Cavrois M, Hilton JF, Roan NR, Averbach S, Takeda M, Chang E, Raman N, Greenblatt R, Shacklett BL, Smith-McCune K

Phenotypic analysis of the unstimulated in vivo HIV CD4 T cell reservoir.

eLife

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

Sequence-independent recognition of the amyloid structural motif by GFP protein family.

Proceedings of the National Academy of Sciences of the United States of America

Xu SCS, LoRicco JG, Bishop AC, James NA, Huynh WH, McCallum SA, Roan NR, Makhatadze GI

SARS-CoV-2-specific T cells exhibit phenotypic features of robust helper function, lack of terminal differentiation, and high proliferative potential.

Cell reports. Medicine

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

Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy.

Cell reports

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

Seminal plasma-derived extracellular vesicle fractions from HIV-infected men exhibit unique miRNA signatures and induce a pro-inflammatory response in cells isolated from the female reproductive tract.

Journal of virology

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

Loss of Pre-Existing Immunological Memory among HIV Infected Women Despite Immune Reconstitution with Antiretroviral Therapy.

The Journal of infectious diseases

Thomas A, Hammarlund E, Gao L, Holman S, Michel KG, Glesby M, Villacres MC, Golub ET, Roan NR, French AL, Augenbraun MH, Slifka MK

HIV efficiently infects T cells from the endometrium and remodels them to promote systemic viral spread.

eLife

Ma T, Luo X, George AF, Mukherjee G, Sen N, Spitzer TL, Giudice LC, Greene WC, Roan NR

Tissue memory CD4+ T cells expressing IL-7 receptor-alpha (CD127) preferentially support latent HIV-1 infection.

PLoS pathogens

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

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.

Human reproduction (Oxford, England)

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

Measuring the contribution of ?d T cells to the persistent HIV reservoir.

AIDS (London, England)

James KS, Trumble I, Clohosey ML, Moeser M, Roan NR, Adimora AA, Joseph SB, Archin NM, Hudgens M, Soriano-Sarabia N

Single-cell Motility Analysis of Tethered Human Spermatozoa.

Bio-protocol

Skinner WM, Mannowetz N, Lishko PV, Roan NR

Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function.

Nature communications

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

Potent and rapid activation of tropomyosin-receptor kinase A in endometrial stromal fibroblasts by seminal plasma.

Biology of reproduction

Martin JW, Chen JC, Neidleman J, Tatsumi K, Hu J, Giudice LC, Greene WC, Roan NR

Structure, function and antagonism of semen amyloids.

Chemical communications (Cambridge, England)

Röcker A, Roan NR, Yadav JK, Fändrich M, Münch J

Semen inhibits Zika virus infection of cells and tissues from the anogenital region.

Nature communications

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

Resident T cells stand up to HIV.

Science immunology

Roan NR

An Optimized and Validated Method for Isolation and Characterization of Lymphocytes from HIV+ Human Gut Biopsies.

AIDS research and human retroviruses

Trapecar M, Khan S, Roan NR, Chen TH, Telwatte S, Deswal M, Pao M, Somsouk M, Deeks SG, Hunt PW, Yukl S, Sanjabi S

Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+ T Cells.

Cell reports

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

Semen amyloids participate in spermatozoa selection and clearance.

eLife

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

Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells.

PLoS pathogens

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

Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection.

AIDS (London, England)

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

Gallic Acid Is an Antagonist of Semen Amyloid Fibrils That Enhance HIV-1 Infection.

The Journal of biological chemistry

LoRicco JG, Xu CS, Neidleman J, Bergkvist M, Greene WC, Roan NR, Makhatadze GI

Amyloid formation: functional friend or fearful foe?

Journal of internal medicine

Bergman P, Roan NR, Römling U, Bevins CL, Münch J

Evaluation of EPI-X4 as a urinary peptide biomarker for diagnosis and prognosis of late acute GvHD.

Bone marrow transplantation

Müller JA, Zirafi O, Roan NR, Lee SJ, Münch J

Friend or Foe: Innate Sensing of HIV in the Female Reproductive Tract.

Current HIV/AIDS reports

Roan NR, Jakobsen MR

Improving preclinical models of HIV microbicide efficacy.

Trends in microbiology

Roan NR, Münch J

Semen enhances HIV infectivity and impairs the antiviral efficacy of microbicides.

Science translational medicine

Zirafi O, Kim KA, Roan NR, Kluge SF, Müller JA, Jiang S, Mayer B, Greene WC, Kirchhoff F, Münch J

Liquefaction of semen generates and later degrades a conserved semenogelin peptide that enhances HIV infection.

Journal of virology

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

Interaction of fibronectin with semen amyloids synergistically enhances HIV infection.

The Journal of infectious diseases

Roan NR, Chu S, Liu H, Neidleman J, Witkowska HE, Greene WC

Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen.

Nature communications

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

Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts.

Human reproduction (Oxford, England)

Chen JC, Johnson BA, Erikson DW, Piltonen TT, Barragan F, Chu S, Kohgadai N, Irwin JC, Greene WC, Giudice LC, Roan NR

Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses.

Nature nanotechnology

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

[Role of semen-derived amyloid fibrils as facilitators of HIV infection].

Medecine sciences : M/S

Roan NR, Cavrois M, Greene WC

Peptides released by physiological cleavage of semen coagulum proteins form amyloids that enhance HIV infection.

Cell host & microbe

Roan NR, Müller JA, Liu H, Chu S, Arnold F, Stürzel CM, Walther P, Dong M, Witkowska HE, Kirchhoff F, Münch J, Greene WC

Naturally occurring fragments from two distinct regions of the prostatic acid phosphatase form amyloidogenic enhancers of HIV infection.

Journal of virology

Arnold F, Schnell J, Zirafi O, Stürzel C, Meier C, Weil T, Ständker L, Forssmann WG, Roan NR, Greene WC, Kirchhoff F, Münch J

Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI.

Retrovirology

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

Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer of viral infection).

The Journal of biological chemistry

Roan NR, Sowinski S, Münch J, Kirchhoff F, Greene WC

T cell responses in the absence of IFN-gamma exacerbate uterine infection with Chlamydia trachomatis.

Journal of immunology (Baltimore, Md. : 1950)

Gondek DC, Roan NR, Starnbach MN

The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection.

Journal of virology

Roan NR, Münch J, Arhel N, Mothes W, Neidleman J, Kobayashi A, Smith-McCune K, Kirchhoff F, Greene WC

Conquering sexually transmitted diseases.

Nature reviews. Immunology

Starnbach MN, Roan NR

Discovery of CD8+ T cell epitopes in Chlamydia trachomatis infection through use of caged class I MHC tetramers.

Proceedings of the National Academy of Sciences of the United States of America

Grotenbreg GM, Roan NR, Guillen E, Meijers R, Wang JH, Bell GW, Starnbach MN, Ploegh HL

Immune-mediated control of Chlamydia infection.

Cellular microbiology

Roan NR, Starnbach MN

Antigen-specific CD8+ T cells respond to Chlamydia trachomatis in the genital mucosa.

Journal of immunology (Baltimore, Md. : 1950)

Roan NR, Starnbach MN

Monitoring the T cell response to genital tract infection.

Proceedings of the National Academy of Sciences of the United States of America

Roan NR, Gierahn TM, Higgins DE, Starnbach MN

Developmental regulation of Chlamydia trachomatis class I accessible protein-1, a CD8+ T cell antigen.

The Journal of infectious diseases

Balsara ZR, Roan NR, Steele LN, Starnbach MN

The Listeria monocytogenes lemA gene product is not required for intracellular infection or to activate fMIGWII-specific T cells.

Infection and immunity

D'Orazio SE, Velasquez M, Roan NR, Naveiras-Torres O, Starnbach MN