I have a strong background in reproductive neuroendocrinology. My graduate work focused on sex differences in the regulation of LH secretion in reflex ovulators. I developed a sensitive radioimmunoassay to allow the measurement of LH in small volumes of serum, which lead to the first characterization of LH pulses and the LH surge in a reflex ovulator. This was followed by a postdoctoral fellowship, during which I conducted some of the earliest studies examining the regulation of FSH synthesis by activin and inhibin. I continued my focus on the field of neuroendocrinology when I joined the faculty at Harvard Medical School/Brigham and Women’s Hospital (BWH) in Neurosurgery; I conducted studies on the hormonal regulation of meningiomas and pituitary adenomas. I have also taken part in genome-wide studies to identify mutations of brain tumors using whole exome sequencing and RNA-Seq.
Since joining the Laboratory of Reproductive Neuroendocrinology under Dr. Kaiser’s leadership in the Division of Endocrinology at BWH, I have actively participated in research related to the identification and characterization of genetic mutations in G protein-coupled receptors involved in reproduction (KISS1R, PROKR2, and TACR3), occurring in patients with defects in the neuroendocrine control of reproduction, which has led to a better understanding of the structure-function relationships of GPCRs. I have had a long-standing interest in studying the molecular and cellular mechanisms regulating the pulsatile release of GnRH release and, more recently, kisspeptin, and how this is influenced by energy balance. I also serve as the Laboratory Director for the Division of Endocrinology and for the Laboratory of Reproductive Neuroendocrinology as well as the co-Chair of the BWH IACUC Committee and a voting member of the BWH IRB Committee. In addition, I am an adjacent assistant professor at the University of Massachusetts Medical School in the Department of Neurosurgery.
I completed my medical school and residency at Rutgers Robert Wood Johnson in New Jersey, and I am currently a clinical/research fellow in endocrinology at Brigham & Women’s Hospital.
I have an interest in both reproductive endocrinology and neuroendocrinology, with my primary research focus looking at the cortisol response in women during menopausal aging in relation to sleep disturbances and hot flashes. My other research projects include looking at how menopausal hot flashes are affected by elevated prolactin levels, and the clinical presentation and outcomes in patients with confirmed gonadotroph pituitary adenomas using transcription factors for classification.
I completed my PhD thesis with Prof. Stacia Sower in biochemistry at the University of New Hampshire in 2017, which centered on the evolution of the hormones and receptors of the hypothalamic-pituitary-gonad axis in sea lamprey, a basal vertebrate. I was awarded a Vaadia-BARD (Binational Israel-USA Agriculture Research and Development fund) Postdoctoral Fellowship to continue the characterization of Nile tilapia reproductive hormones with Prof. Berta Sivan at the Hebrew University of Jerusalem in Israel.
I joined Dr. Kaiser’s lab in February 2020. I am currently working to identify the mechanism by which pituitary gonadotropes decode GnRH pulse frequencies in order to differentially express LH or FSH. Using a controlled perifusion device, prior studies have shown that 30 minutes GnRH pulse frequencies preferentially activate LH and inhibit FSH transcription via Gq signaling, whereas 2-hour pulses result in transcription of FSH via Gs. My specific goal is to identify if GnRH pulse frequency and GnRHR density contribute to GnRHR preferential coupling to Gs or Gq signaling by FRET analysis.
I graduated from Dickinson College with a B.S. in Biology and moved to Boston to join Dr. Kaiser’s Neuroendocrinology lab in July 2015 as a Technical Research Assistant.
I help and support fellow lab members in the lab with their day-to-day activities. Throughout my experiences in the lab, I have gained expertise in cell culture, mouse genotyping, reproductive phenotyping, small animal surgery, quantitative real-time PCR and Western blot analysis. I was also privileged to be given my own project which is focused on identifying the molecular mechanisms by which pulsatile gonadotropin releasing hormone (GnRH) differentially regulates the expression of the gonadotropin hormones, luteinizing hormone and follicle-stimulating hormone. Our preliminary studies in vitro suggest that GnRH receptor couples to both Gq/11 and Gs signaling pathways and are differentially activated by pulsatile GnRH. For the in vivo studies, I generated a transgenic mouse model in which the Gq/11 signaling pathway is specifically deleted from the gonadotrope cells in the anterior pituitary gland using the Cre-Lox system. The results in vivo showed that the female Gq/11 knockout (KO) mice do not complete pubertal maturations and are anestrus. These results showed that Gq/11 clearly plays a role in the regulation of gonadotropin synthesis of mice and that the gonadotrope specific Gq/11 deletion prevents pubertal maturation.
After graduating in Medicine in 2006 at Federal University of Ceara, Brazil and completing residency in Internal Medicine and Endocrinology and Metabolism at Sao Paulo Federal University (2008-2012), I undertook a PhD. research program at Sao Paulo University, Brazil under the mentorship of Dr. Ana Claudia Latronico. My PhD thesis on the genetic aspects of patients with familial and sporadic central precocious puberty was honored with a CAPES award from the Brazilian Ministry of Education.
In October 2018, I joined Dr. Kaiser’s laboratory as a postdoctoral research fellow. My main interest centers in the clinical, genetic and mechanistic aspects of central precocious puberty (CPP). With the recent discovery of novel mutations in the DLK1gene in families with CPP (Gomes L.et al. Journal Clinical of Endocrinology and Metabolism, 2018), I have focused on understanding the role and mechanisms of action of DLK1 in the neural network controlling puberty initiation, by using Dlk1 global and conditional (tissue-specific) deficient mouse models. I am currently characterizing the pubertal phenotype and conducting experiments to identify possible partners and/or targets of Dlk1 action in the regulation of puberty initiation in vivo.
I am a Technical Research Assistant working under Dr. Ana Paula Abreu Metzger MD PhD. I am from Rochester, Minnesota, and went to Colby College in Waterville, Maine. I graduated from Colby with a B.A. in Biology with a concentration in Cellular/Molecular Biology and Biochemistry, and I started working here at BWH in October 2020. Dr. Abreu Metzger has a variety of ongoing projects that I have been assisting with. Since my start date, we have been continuing her ongoing investigation into the biochemical mechanisms responsible for Central Precocious Puberty (CPP). She has identified MKRN3 mutations as a driver for this disease, and to build from this I have been modeling identified MKRN3 mutations in patients with CPP through a mutagenesis experiment. We also have been and are continuing to explore clinical and genetic connections between patients with corticotroph adenomas, specifically regarding mutations in USP8 and other ubiquitin-related mutations. Looking forward, our newest project will consist of exploring adrenocortical carcinomas (ACC), specifically how ACC cells evade common chemotherapeutic treatments and what avenues should be taken to combat metastasis.
I received a Bachelor of Science degree from Roger Williams University and for 5 years served as the director of the Specialty Assay Research Core (SARC) and subsequently joined Dr. Kaiser’s lab as a research technician.
My role in Dr. Kaiser’s lab involves sequencing patient DNA for mutations in genes involved in reproductive disorders. I also perform ELISA assays, some animal procedures and maintain the inventory of biological specimens used in research projects. I serve as the laboratory’s safety and radiation officer. I’m also a coordinator involved in the IRB submission for some clinical trials. I’m involved in assisting physicians with the administration of radioiodine uptake and therapies.
I graduated in Medicine and Surgery and obtained a PhD in Molecular Endocrinology at the University of Naples, Italy. I worked from 2015 to 2019 as a Clinical and Research Fellow at Paris-Sud University, France, and moved to Boston to join the Kaiser laboratory in November 2019.
My activities include either clinical assignments and missions, or research activities. Currently he is conducting clinical and molecular research on the regulation of gonadotrope axis and fertility, and more broadly on hypothalamus and pituitary pathophysiology. He is author of several peer-reviewed articles and reviews, that are summarized in the following link: https://www.ncbi.nlm.nih.gov/sites/myncbi/1XGje6Oe0Vakt/bibliography/40630580/public/?sort=date&direction=asc ending). He is member of five Endocrine Societies, he is regularly invited to international conferences and he actively participates in reviewing activities for multiple Journals. Finally, he is involved in teaching activities. He has been training medical students at the Medicine Faculty of Paris-Sud University, he has directed five theses for undergraduate medical students, and he has written 13 chapters in Endocrine textbooks.
In November 2019 I have joined the Laboratory of the Division of Endocrinology, Diabetes and Hypertension at the Brigham and Women’s Hospital. My project is to contribute to the understanding of the regulation of the gonadotrope axis by Makorin-RING finger protein 3 (MKRN3). The hosting laboratory first demonstrated that MKRN3 is a major inhibitor of the gonadotrope axis, and genetic abnormalities of MKRN3 are associated to precocious puberty through anticipation of gonadotrope axis activation. The mechanism by which MKRN3 inhibits the gonadotrope axis is currently under investigation, and the hosting lab developed a mouse model lacking Mkrn3. His project aims at using a pharmacologic approach to agonize/antagonize some key components of the gonadotrope axis, such as GnRH, kisspeptin and neurokinin B and to identify at which level Mkrn3 is regulated.
I received my MSc from University of Florence, Italy and most recently a PhD from Queen Mary University of London, UK in January 2020. My PhD research focused on discovery and characterization of genetic mutations affecting the pubertal timing. This work has been published in a number of peer-reviewed journals including JCI Insight and Human Molecular Genetics. In recognition of my research, I won the Henning Andersen Prize for best clinical and experimental abstract from The European Society of Pediatric Endocrinology (ESPE) in 2018. I am especially interested in GnRH neuronal migration during embryogenesis orchestrating the onset of puberty.
I joined the Kaiser lab as a postdoctoral fellow in March 2020. Currently my projects are focused on furthering the understanding of MKRN3 and DLK1 in the regulation of pubertal timing using hiPSCs and in vivo models.
I received my MD degree from Chongqing Medical University, China and a PhD degree from National University of Singapore, Singapore. I had postdoctoral training at University of Iowa and Stony Brook University. I had my medical residency training at Mount Sinai School of Medicine (North General) Program and a fellowship training at Brigham and Women’s Hospital, Harvard medical School.
I am an endocrinologist at Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Associate clinical director of neuroendocrine program, and an assistant professor of Medicine at Harvard Medical School, Boston. I am a physician scientist. I have been doing patientcare as well as clinical and translational research. My research interests focus on immune checkpoint inhibition-related endocrine toxicities, neuroendocrine disorders, and neuroendocrine regulation of reproduction. I have numerous publications in high rank peer-review journals including The Lancet Diabetes and Endocrine Review, Endocrinology, JAMA oncology, Cancer Immunology Research, Cancer Clinical Research, Cancer, molecular endocrinology, and Endocrinology. I am Ad hoc Reviewer for many journals. I am awarded K08 funding from NIH. I serve as an NCI Investigational Drug Steering Committee -Immunotherapy Working Group.
I completed my PhD in Neuroscience at the University Pierre and Marie Curie (Paris, France), in Dr. Mhaouty-Kodja’s laboratory where I studied the mechanisms underlying the regulation of pubertal onset and the expression of female sexual behavior by estradiol. My research interests focus on the field of neuroendocrinology, particularly on understanding the mechanisms underlying the regulation of reproductive function, including puberty initiation and fertility, as well as unraveling the neurodevelopmental mechanisms underlying neuroplasticity during puberty and sex differences in these processes.
My current postdoctoral research project in Dr. Kaiser laboratory focuses on understanding the role and mechanisms of action of MKRN3 in the regulation of puberty initiation. To this end, I am using a combination of in vivo (Mkrn3 deficient mouse model) and in vitro (human inducible pluripotent stem cell (hiPSC)-derived hypothalamic cell model) approaches to identify the targets of MKRN3 and elucidate the role of MKRN3 in neuronal plasticity during pubertal development.
I attended medical school at the University of Connecticut and subsequently completed pediatric residency at Hasbro Children’s Hospital and pediatric endocrinology fellowship at Boston Children’s Hospital.
I am currently a research fellow in Dr. Kaiser’s laboratory as well as an attending physician in the Division of Endocrinology at Boston Children’s Hospital and an Instructor of Pediatrics at Harvard Medical School. As a physician-scientist, I investigate observations from my clinical practice to understand at the molecular level how genetic variants affect the neurobiology of puberty and reproductive disorders. I initially studied the potential regulation of Makorin Ring Finger Protein 3 (MKRN3) by leptin, and more recently generated a novel mouse model with Mkrn3 overexpression in the mouse hypothalamus, demonstrating the ability of Mkrn3 overexpression to delay pubertal onset in female mice. I am currently using this model to further understand the mechanism of action of MKRN3 and how it may be involved potentially in delayed puberty in children.
I graduated from FCMMG with an MD degree in 2019 and moved from Brazil to Boston to join Dr. Kaiser’s Neuroendocrinology Lab in January 2020 as a research trainee. Since then, I have been gaining expertise in RNA extraction, cDNA synthesis, quantitative PCR, DNA methylation studies, Western blot analysis, and mammalian cell culture. I have been working with Dr. Ana Paula Metzger in projects related to ACTH secreting tumors and glucocorticoid resistance syndromes. Our goal is to identify novel genes that would help us better understand the underlying pathophysiology of patients that present with hypercortisolism and do not develop Cushing’s disease.