Understanding the genetic basis of reproductive and developmental biology
Our research brings together human genetics, reproductive and developmental biology, and primate genomics to understand how genetic variation influences biological function and disease. These areas are deeply interconnected, and discoveries in one often provide the tools, models, or biological insights that drive another.
a common foundation across our work
Developing new ways to identify, analyze, and interpret genetic variation has been a central focus of the Conrad Lab for more than two decades. We combine statistical genetics, computational biology, and experimental genomics to move from variant discovery to biological interpretation, connecting genotype to phenotype across cells, tissues, individuals, populations, and species.
our research areas
Discovering the genetic causes of male infertility and determining how genetic variation disrupts reproductive development and function.
A cornerstone of this work is GEMINI (GEnetics of Male INfertility Initiative), an international consortium bringing together male infertility cohorts from around the world. This collaborative effort provides the scale and diversity needed to investigate the highly heterogeneous genetic causes of male infertility.
Using exome and whole-genome sequencing, we discover rare genetic variants associated with spermatogenic failure and other reproductive phenotypes. Our work extends beyond gene discovery to investigate when and how disease-associated variants act, from embryonic and fetal development through adult spermatogenesis. By combining human genetics with functional and genomic studies, we aim to understand the mechanisms that connect genetic variation to reproductive disease.
Increasingly, these discoveries are moving from research into clinical genetics. We are working with ClinGen to establish evidence-based gene–disease relationships for male infertility, helping translate discoveries from large-scale genetic studies into clinically interpretable knowledge. Our efforts also helped establish reproductive disease as a distinct clinical domain within ClinGen, creating a framework for the systematic evaluation of genes underlying male infertility and other reproductive disorders.
Mapping the cellular and molecular programs that build the testis, and understanding how their disruption leads to infertility and disease.
We study how the cellular landscape of the testis is established during development, how it changes across the lifespan, and how disruptions in these processes lead to disease. Using single-cell RNA sequencing and spatial transcriptomics, we map cell populations, developmental trajectories, gene-expression programs, and their organization within intact tissue.
We also develop quantitative approaches to connect molecular changes with tissue structure and pathology. SATINN (Segmenting and Assigning Testis cell types from histology images using Neural Networks) uses deep learning to automate the analysis of testis histology images, allowing us to characterize cellular and tissue-level phenotypes at scale.
Because critical stages of human testis development cannot be studied directly, nonhuman primates provide an important comparative model. Through NHP dGTEx (Nonhuman Primate Developmental Genotype-Tissue Expression), developmental data from macaques and marmosets allow us to investigate otherwise inaccessible stages of testis development and provide biological context for interpreting genetic findings in human reproductive disease.
This framework is also opening new directions in testicular germ-cell cancer, where we are investigating how germline genetic variation and the testicular microenvironment may influence progression from developmentally arrested germ cells to pre-invasive lesions and invasive disease.
Using comparative, developmental and population genomics to understand primate biology and illuminate human biology.
Through NHP dGTEx, we study how gene expression and regulation change across development in rhesus macaques and common marmosets. As part of the broader developmental GTEx initiative, NHP dGTEx complements human dGTEx by extending developmental genomic studies into prenatal stages that cannot readily be studied in humans. Integrating genomic, transcriptomic, single-cell, spatial, and other molecular data across species allows us to identify conserved and species-specific features of primate development and build a more complete picture of how gene regulation changes across the lifespan.
Our work in the common marmoset also extends to population and genome biology. The MCC (Marmoset Coordinating Center) serves as a centralized resource for the U.S. marmoset research community, integrating genomic, pedigree, demographic, and colony data from breeding centers across the country. The MCC coordinates requests for research animals and works with breeding centers to facilitate animal transfers, helping investigators identify animals appropriate for their research while supporting genetically informed breeding and colony management.
These activities also create a unique population-scale genomic resource. By characterizing genetic diversity, ancestry, population structure, and relatedness across the U.S. research population, we can address fundamental questions in marmoset genetics while improving the use of the marmoset as a genetically informed model organism. More broadly, we develop genomic resources and approaches for studying genetic variation, mutation, relatedness, and genome structure in marmosets and other primates.
