Researcher Spotlights

Researcher Spotlight - Dr. Winifred Mak

Winifred Mak, MD, PhD

Grant Project Title:

Establishment and characterization of miscarriage-specific human trophoblast stem cells

Grant Amount:

$40,000

Significance:

750,000 to 1,000,000 miscarriages happen in the United States annually. For couples who experience pregnancy loss, the cause is usually cytogenetic in 60% of cases, such as trisomy and monosomy. However, the cause of the remaining euploid miscarriages is usually not found. Therefore, there is a significant need for more studies to investigate new causes of human pregnancy loss, especially recurrent miscarriages, where 50% of couples will not find a cause. To elucidate the molecular mechanisms of miscarriages in humans, new tools are necessary to study these events as up until now; one significant barrier is the limited amount of tissue, mainly chorionic villi, available for analysis. Prior studies on early human placentation have primarily relied on transformed trophoblast cell lines or primary human trophoblast cells purified from the early placenta, which cannot be propagated. Therefore, a proliferating primary trophoblast cell culture system to study human miscarriage is an essential technical advancement to overcome these past research barriers. Recently, researchers have established control human trophoblast stem (TS) cell lines from first-trimester chorionic villi from normal pregnancies and human blastocysts from IVF. Therefore, our project aims to establish human TS cells from first-trimester miscarriage chorionic villi as a new tool to elucidate the pathophysiology of unexplained first-trimester miscarriages and ultimately find new causes of recurrent miscarriages.
This ASRM Research Institute grant has been instrumental in providing me with the essential funds to carry out the necessary pilot experiments required to establish the feasibility of this high-risk, high-reward research project. Furthermore, the data generated from this grant has provided the crucial scientific support and feasibility data required to submit a competitive R01 grant and to help me towards my long-term career goal to be an independent physician-scientist. It is hard to express in a few words how grateful I am to ASRM Research institute for providing this grant to me as it allows me to ‘stay in the research game’ and one day translate my bench research to help couples with recurrent miscarriages.
Winifred Mak, MD, PhD
Associate Professor, UT Health Sciences at San Antonio and Dell Medical School (UT Austin)

Researcher Spotlight - Dr. Gary Smith

Gary Smith, PhD, HCLD

Grant Project Title:

Human Embryo Mosaicism: Towards Understanding Longitudinal and Developmental Genetic Concordance Between Embryonic Trophectoderm, Inner Cell Mass, and Stem Cells

Grant Amount:

$666,000

Significance:

Our hypothesis is that blastocyst regional cell genetic concordance is low, embryonic mitotic segregation errors are frequent, and that collectively, these biological factors contribute to embryonic mosaicism and limitations in predicting offspring genetic normalcy. This hypothesis is being addressed with two specific aims: 1) to elucidate regional genetic concordance/discordance within human preimplantation blastocysts trophectoderm, inner cell mass, and resulting human embryonic stem cells with single cell-sequencing; and 2) to quantify the incidence of age-related human oocyte/embryo meiotic and mitotic nondisjunctions as they contribute to blastocyst mosaicism.



These studies represent first-in-field approaches to systematically and longitudinally identify developmental and genetic events in human embryos that must be understood to allow confidence in preimplantation genetic testing-aneuploidy (PGT-A) use and interpretations. These data will guide the future of PGT-A and have an immediate impact of eliminating knowledge-gaps in PGT-A, mosaicism, and decision-making for reproductive healthcare providers, patients, and the general population.
Gary D. Smith, Ph.D., H.C.L.D.
Professor of Ob/Gyn, Physiology, and Urology
Director of MStem Cell Lab
Director of Reproductive Sciences Program
University of Michigan

Researcher Spotlight - Dr. Werner Neuhausser

Werner Neuhausser, M.D., Ph.D.

Grant Project Title:

Identification of transcriptomic and epigenetic coordinates for post-implantation human embryonic development

Grant Amount:

$666,000

Significance:

Post-implantation human embryonic development beyond the blastocyst stage is pertinent to a variety of disorders in human reproduction such as implantation failure, fetal defects, placental insufficiencies and early pregnancy loss. However, our knowledge of cell-lineage decisions in the post-implantation human embryo remains severely limited and there is a critical need to explore the molecular control underlying the formation of trophoblast, epiblast and hypoblast lineages and the events surrounding implantation and gastrulation. In addition, it remains one of the premier goals of reproductive medicine to identify effective biomarkers that predict successful post-implantation development and pregnancy following uterine transfer of in-vitro fertilization (IVF) embryos. Our long-term goal is to understand cellular differentiation in the post-implantation human embryo at the molecular level and develop novel genomic predictors of pregnancy outcomes for pre-implantation testing of IVF embryos. This project aims to delineate the transcriptomic and epigenomic changes underlying human post-implantation lineage development and use this dataset to develop transcriptional and epigenetic predictors of successful implantation and gastrulation using a human post-implantation model in vitro.
We are immensely grateful to the ASRM Research Institute for supporting this project. It is very difficult to obtain funding for this line of research because the NIH currently restricts research projects involving reproductive medicine. As such, the ASRM Research Institute plays an important and unique role in funding basic research in human embryology and this support will unlock the tremendous translational potential in this field going forward. In our case it allows us to use cutting edge single cell multiome sequencing technology to address a fundamental question in reproductive biology – what are the molecular building blocks of a successful post-implantation human embryo and how can these single cell genomic technologies be used to identify high implantation potential embryos prior to uterine transfer?
Werner Neuhausser, MD PhD
Instructor in Obstetrics, Gynecology and Reproductive Biology
Division of Reproductive Endocrinology & Infertility
Beth Israel Deaconess Medical Center
Harvard Medical School

Researcher Spotlight - Dr. Eve Feinberg



Eve Feinberg, M.D.

Grant Project Title:

Characterizing Fertility Concerns among Women in Academic Medicine and Evaluating the Economic Impact of Fertility Preservation for Deferred Reproduction

Grant Amount:

$50,000

Significance:

Although women are more likely than men to pursue a career in academic medicine, they also tend to leave academic medicine, reduce their work hours, or reroute their careers during their childbearing years. In addition, many female physicians delay childbearing, and studies have documented higher rates of infertility, obstetric complications, and childlessness in female physicians relative to the general population. Female physicians report high levels of interest in fertility preservation and assisted reproduction technology (ART) options. Two primary factors that may prevent women in academic medicine from undergoing oocyte vitrification at younger ages (≤ 35 years old) include a lack of awareness regarding the importance of age on the efficiency and success of fertility preservation and the high costs of fertility preservation without adequate insurance coverage. The purpose of this project was to investigate and characterize the unique fertility concerns of women in academic medicine and examine female physicians’ understanding of the role of age in determining the efficiency and success of fertility preservation options.
The ASRM research institute grant was instrumental in beginning my work to explore the challenges faced by women in medicine with regard to fertility and family building concerns. The literature has shown a large degree of gender disparity in academic promotion and rank and the theme of fertility and family building and how that has been a contributing factor has previously not been explored. This grant allowed me to do some foundational research upon which I hope to build and really helped to get this project off the ground. I am tremendously appreciative of the support from ASRM in this work.
Eve Feinberg, MD
Associate Professor of OB/GYN, specializing in REI at Northwestern University

 
Click bottom right to view full screen

Researcher Spotlight - Dr. Amanda Kallen



Amanda Kallen, M.D.

Grant Project Title:

Novel, Noncoding-RNA-Mediated Mechanisms for Regulation of Follicular Quantity and Quality

Grant Amount:

$50,000

Significance:

Reproductive health issues as serious as miscarriage, birth defects, and the loss of fertility due to advancing age or exposure to gonadotoxic agents can frequently be traced back to a decline in oocyte quality and/or quantity. Dr. Kallen's studies have the potential to define noncoding RNAs as major regulators of ovarian reserve and are directly related to the NIH Fertility and Infertility Branch’s mission of supporting research that enhances our understanding of normal reproduction and reproductive pathophysiology.




The importance of the ASRM research grant in my career development cannot be overstated. The ASRM grant, which came at a time when I needed bridge funds to “stay in the game” as an REI physician-scientist transitioning to independence, paved the way for me to successfully obtain independent NIH funding. My ASRM funding allowed me to complete ongoing studies, continue building on preliminary data, and successfully respond to critiques from prior R01 submissions. The culmination of these ASRM-supported efforts was an R01 submission which was scored at the first percentile! This work, and this achievement, would simply not have been possible without ASRM’s support, and I am so incredibly grateful for the resources, support, and demonstrated commitment to young physician-scientists by this incredible organization.
Amanda N. Kallen, MD
Associate Professor, Yale Medicine
Division of Reproductive Endocrinology & Infertility
Department of Obstetrics, Gynecology, & Reproductive Sciences