A5090551594- Reproductive Biology and Fertility
- Reproductive System and Pregnancy
- Renal and related cancers
- Ovarian function and disorders
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- FOXO transcription factor regulation
- Sperm and Testicular Function
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Ovarian cancer diagnosis and treatment
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- RNA Research and Splicing
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Virus-based gene therapy research
- Multiple Myeloma Research and Treatments
- Acute Myeloid Leukemia Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Endometriosis Research and Treatment
Massachusetts General Hospital
2017-2023
Harvard University
2017-2023
Boston University
2019
Southwestern Medical Center
2016
The University of Texas Southwestern Medical Center
2014-2016
Harold C. Simmons Comprehensive Cancer Center
2015
Significance All current reversible hormonal contraceptives rely on modulating gonadotropins or sex steroids by acting the hypothalamic–pituitary–gonadal axis. Primordial follicle activation, first step of folliculogenesis, is independent steroids. In this study we show that Müllerian inhibiting substance (MIS) can completely block primordial representing a unique mechanism contraception spares pool quiescent follicles (ovarian reserve). Chemotherapy thought to cause over-recruitment...
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Spermatogenesis is a complex, multistep process that maintains male fertility and sustained by rare germline stem cells. Spermatogenic progression begins with spermatogonia, populations of which express distinct markers. The identity the spermatogonial cell population in undisturbed testis controversial due to lack reliable specific Here we identified transcription factor PAX7 as marker subpopulation Asingle spermatogonia mice. PAX7+ cells were present at birth. Compared adult testis,...
The estrous cycle is regulated by rhythmic endocrine interactions of the nervous and reproductive systems, which coordinate hormonal ovulatory functions ovary. Folliculogenesis follicle progression require orchestrated response a variety cell types to allow maturation its sequela, ovulation, corpus luteum formation, wound repair. Little known about state dynamics ovary during paracrine factors that help this process. Herein, we used single-cell RNA sequencing evaluate transcriptome...
In mammals, females are born with finite numbers of oocytes stockpiled as primordial follicles. Oocytes "reawakened" via an ovarian-intrinsic process that initiates their growth. The forkhead transcription factor Foxo3 controls reawakening downstream PI3K-AKT signaling. However, the identity presumptive upstream cell surface receptor controlling PI3K-AKT-Foxo3 axis has been questioned. Here we show tyrosine kinase Kit reawakening. Oocyte-specific expression a novel constitutively-active...
Endometrial cancer is the most common gynecologic malignancy and fourth in women. For patients whom disease confined to uterus, treatment results successful remission; however, there are no curative treatments for tumors that have progressed beyond uterus. The serine/threonine kinase LKB1 has been identified as a potent suppressor of uterine cancer, but biological modes action this context remain incompletely understood. Here, we shown suppresses tumor progression by altering gene expression...
Müllerian inhibiting substance (MIS/AMH), produced by granulosa cells of growing follicles, is an important regulator folliculogenesis and follicle development. Treatment with exogenous MIS in mice suppresses development prevents ovulation. To investigate the mechanisms which inhibits development, we performed single-cell RNA sequencing whole neonatal ovaries treated at birth analyzed postnatal day 6, coinciding first wave growth. We identified distinct transcriptional signatures associated...
The Mullerian ducts are the anlagen of female reproductive tract, which regress in male fetus response to MIS. This process is driven by subluminal mesenchymal cells expressing Misr2, trigger regression adjacent ductal epithelium. In females, these Misr2+ retained, yet their contribution development uterus remains unknown. Here, we report that persist postnatally rodents, but recede week 37 gestation humans. Using single-cell RNA sequencing, demonstrate ectopic postnatal MIS administration...
Abstract Eighty percent of the estimated 600 million domestic cats in world are free-roaming. These typically experience suboptimal welfare and inflict high levels predation on wildlife. Additionally, euthanasia healthy animals overpopulated shelters raises ethical considerations. While surgical sterilization is mainstay pet population control, there a need for efficient, safe, cost-effective permanent contraception alternatives. Herein, we report evidence that single intramuscular treatment...
Abstract Background: Ivosidenib (IVO) is a first-in-class oral inhibitor of the IDH1 mutant (mIDH) enzyme. In ClarIDHy phase 3 study previously treated patients with mIDH cholangiocarcinoma (CCA), IVO treatment led to improved progression-free survival (PFS) and overall (OS) vs placebo (median PFS: 2.7 vs. 1.4 months OS 10.3 5.1 months, when adjusted for 70% crossover rate; HR, 0.49 [95% CI, 0.34-0.70]; 1-sided P<0.001. Here, we studied dynamics mutations emerging after 6 using ctDNA...
Müllerian-inhibiting substance (MIS), also known as anti-Müllerian hormone, is thought to be a negative regulator of primordial follicle activation. We have previously reported that treatment with exogenous MIS can induce complete ovarian suppression within 5 weeks in mice. To investigate the kinetics return folliculogenesis following reversal suppression, we treated animals recombinant human (rhMIS) protein for 40 days adult female Nu/Nu mice and monitored recovery each type over time....
Abstract Liver receptor homolog-1 (NR5A2) is expressed specifically in granulosa cells of developing ovarian follicles where it regulates the late stages follicle development and ovulation. To establish its effects earlier trajectory follicular development, NR5A2 was depleted from murine primordial primary follicles. Follicle populations were enumerated neonates at postnatal day 4 (PND4) coinciding with end formation pool. The frequency PND4 conditional knockout (cKO) ovaries greater...
Abstract Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population ovarian cancer cells both in vivo and vitro. We have previously that its receptor, MISRII, is expressed majority serous adenocarcinomas. However determinants response pathways elicited by MIS treatment difficult elucidate due heterogeneity tumors across patient within each sample. To address this complexity we developed an assay which immune are isolated from ascites recurrent...
Abstract Background: Epithelial ovarian cancers are the fifth leading cause of cancer-related deaths in American women, with a five-year overall survival rate for patients diagnosed at advanced stages less than 30%. High-grade serous (HGSOCs), most common histologic subtype, often initially responds to platinum-based chemotherapy. However, over 80% experience chemoresistant recurrence advanced-stage disease. Methods: We have established 40 patient-derived HGSOC cell lines from ascites...