# Sex, Gender, and HIV Transmission: Defining the Impact of Biological Sex and Sex Hormones on Epithelial and Immune Cell Transcriptomics and HIV Transmission in Human Rectal Tissues

> **NIH NIH K23** · EMORY UNIVERSITY · 2023 · $172,316

## Abstract

Project Summary/Abstract
Despite a disproportionately high burden of HIV infection among transgender women and transgender men in
the US, gender minorities remain underrepresented in HIV prevention research. While many transgender
individuals utilize feminizing and masculinizing hormones, there are critical knowledge gaps in our mechanistic
understanding of the effects of gender-affirming hormone therapy on the rectal mucosal environment, a critical
site of vulnerability to HIV infection. This is of paramount importance, as biological sex and sex hormones
mediate effects on epithelial and immune cell function through their influence on transcriptional activity of the
cell, and these effects could alter the susceptibility of the rectal mucosa to HIV infection. The Specific Aims of
this proposal are to compare sex-specific, spatially localized gene expression patterns of rectal mucosal immune
and epithelial cell subpopulations between cisgender men and cisgender women utilizing spatial transcriptomics
integrated with single cell RNA sequencing (Aim 1), to define the single cell transcriptomic signatures of rectal
mucosal cellular subsets from cisgender men and cisgender women following ex vivo sex hormone exposure
(Aim 2), and to use the HIV explant challenge model to examine the impact of ex vivo sex hormone treatment
on rectal tissue susceptibility and host mucosal immune responses to HIV infection (Aim 3). This research
strategy will facilitate a 5-year career development and training plan that will enable Dr. Grimsley Ackerley to
build upon her prior research experience and gain critical mentored research training in: 1) Bioinformatics and
Transcriptomic Data Analyses, 2) Mucosal Immunology and HIV transmission, and 3) the Conduct of Sex- and
Gender-Based HIV Research. To achieve these training aims, Dr. Grimsley Ackerley has assembled a
multidisciplinary mentorship team with expertise in mucosal immunology, sex hormone biology, single cell and
spatial transcriptomic technologies, sex- and gender-based research, and biostatistics. This proposal will
capitalize on a robust research environment at Emory University and will be supported by resources available
through The Hope Clinic of the Emory Vaccine Center and the Emory National Primate Research Center.
Dr. Grimsley Ackerley’s long-term career goal is to lead a successful and independent translational mucosal
immunology program that specializes in the use of genomics applications and the ex vivo HIV explant challenge
model to better understand biologic and immunologic factors that influence mucosal HIV susceptibility among
gender and sexual minority populations. Achievement of this long-term goal will be made possible through the
completion of the proposed K23 research aims and training plan, along with the support garnered from the highly
experienced mentorship team. This proposal will begin to address, mechanistically, the effects of biological sex
and gender-affirming hormone therapy on the...

## Key facts

- **NIH application ID:** 10700594
- **Project number:** 1K23AI177081-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Cassie Grimsley Ackerley
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $172,316
- **Award type:** 1
- **Project period:** 2023-07-19 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10700594

## Citation

> US National Institutes of Health, RePORTER application 10700594, Sex, Gender, and HIV Transmission: Defining the Impact of Biological Sex and Sex Hormones on Epithelial and Immune Cell Transcriptomics and HIV Transmission in Human Rectal Tissues (1K23AI177081-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10700594. Licensed CC0.

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