Table 4: Meet the SRI Distinguished Speaker

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Ursula Kaiser, MD

What is Your Current Position?

I am Chief of the Division of Endocrinology, Diabetes, and Hypertension at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School, Boston, MA. I am also the Program Director for an NIH K12 BIRCWH (Building Interdisciplinary Research Careers in Women’s  Health) Award and the Principal Investigator of a T32 Training Grant in Academic Endocrinology. I also direct a basic/translational lab studying the neuroendocrine regulation of puberty and reproduction. I see patients with neuroendocrine disorders and some patients with reproductive endocrine disorders.

What are your current research endeavors and/or other academic contributions?

I am a physician-scientist in the fields of reproductive neuroendocrinology and pituitary biology, with a background in basic and translational research. Both my clinical and research interests focus on reproductive neuroendocrinology. I have been on the faculty at BWH for over 20 years and have been supported by extramural NIH funding throughout that time, investigating the neuroendocrine regulation of reproduction, the regulation of GnRH secretion across pubertal maturation, and the transcriptional control of the gonadotropin genes. I am currently PI on two R01 grants and on a T32 Training Grant in Academic Endocrinology, as well as Research Program Director of an NIH K12 Building Research Careers in Women’s Health (BIRCWH) training program. My studies include research focused on G protein-coupled receptors (GPCRs) and their cognate ligands involved in the neuroendocrine control of human reproduction. Early in my career, I cloned and characterized the rat GnRHR and elucidated its signaling mechanisms. I was among the first to study the effects of human mutations in the GnRHR on its cell surface expression, ligand binding, and signaling capacity to activate LH and FSH. A major focus of my research is to elucidate the mechanisms underlying GnRH pulse frequency-dependent differential regulation of gonadotropin gene expression and thereby LH and FSH synthesis and secretion, relevant to reproductive disorders in women such as hypothalamic amenorrhea and polycystic ovarian syndrome.  In more recent years, I have studied loss-of-function mutations identified in KISS1R, PROKR2, and NK3R in patients with disorders of GnRH production. This translational research has involved clinical and laboratory observations in humans, investigation in mouse models, and laboratory studies, to elucidate the molecular and biological underpinnings of these disorders.  I have also studied genetic and molecular causes of central precocious puberty, demonstrating potentiated signaling by mutant kisspeptin and mutant KISS1R in patients with CPP. More recently, using whole exome sequencing in patients with familial CPP, my laboratory identified novel loss-of-function variants in the gene MKRN3, a gene not previously linked to pubertal physiology and suggested to act as an inhibitory “brake” for GnRH release. Many of our efforts currently focus on elucidating the targets and mechanisms of action of this new player in GnRH regulation.

What has been the most pivotal moment in your career?

I would have to say the discovery of MKRN3 as an important player in puberty. Mutations in MKRN3 are the most common genetic cause of central precocious puberty identified to date, accounting for almost half of all cases of familial central precocious puberty. MKRN3 is the first inhibitor of GnRH identified to date. Thus, this discovery has both important clinical implications and can help lead us to better understanding the fundamental mechanisms controlling GnRH secretion. This was also a pivotal moment because it reflected the culmination of a longterm collaboration with my colleague Ana Claudia Latronico, it has helped to launch the career of my mentee, Ana Paula Abreu Metzger, and I hope will also help to launch the careers of other current members of my research group.

What is one piece of advice you would give to a trainee?

When selecting a research project for your training:

• Pick a good mentor.
• Pick an important problem to solve.
• Work hard.
• Remember the “golden rule”.  

Randy Schekman, PhD

What is Your Current Position?

University Professor in the Dept of Cell and Molecular Biology and Investigator , Howard Hughes Medical Institute, University of California, Berkeley

What are your current research endeavors and/or other academic contributions?

My research concerns the mechanism of membrane assembly and vesicular traffic in eukaryotic cells. Our current focus is on the biogenesis of extracellular vesicles, exosomes, and the means by which small RNA molecules are sorted into exosomes.

What has been the most pivotal moment in your career?

I have had many special moments in my career, but the stand out one was when one of my first graduate students, Peter Novick, first isolated and characterized yeast mutants defective in protein secretion. These mutants and their wild type counterpart gene products allowed my lab to uncover key mechanistic aspects of protein translocation across membranes and sorting of membrane and secretary proteins into transport vesicles.

What is one piece of advice you would give to a trainee?

Pick an important problem that has yet to be understood, choose the simplest appropriate experimental system and approach, and then focus relentlessly on solving the problem.