Meet the Endocrinologist: Ursula Kaiser, expert in neuroendocrine regulation of puberty

Meet Ursula Kaiser, Professor at Harvard Medical School and Chief of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital. Her research is focused on neuroendocrine regulation of puberty, reproductive health and fertility. She has been awarded the SfE International Medal and will be delivering her Medal Lecture at SfE BES 2018, 19-21 November in Glasgow. In our latest interview, she tells us more about her work and what she is looking forward to at the SfE BES 2018 conference.

Can you tell us a little about your current position and research?

At Harvard Medical School and as Chief of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital, I lead and direct a group of over 60 clinical and research endocrinologists at a large academic medical center. My laboratory studies the genetic and molecular mechanisms underlying the neuroendocrine regulation of reproductive development and function, with an emphasis on the mechanisms regulating gonadotropin-releasing hormone (GnRH) and gonadotropin production. We use translational approaches including clinical and laboratory observations in humans, investigations in mouse models, and molecular and cellular studies to elucidate the molecular and biological underpinnings of reproductive disorders.

Can you tell us a little about what inspired you into endocrinology?

I grew up in Canada, where I received my undergraduate degree in biology at University of New Brunswick followed by my medical degree at University of Toronto. Early in medical school, I became fascinated by the feedback loops of endocrinology and by the many systems affected by hormones, and was quickly convinced that endocrinology was my calling. I completed my clinical training and licensure in internal medicine and in endocrinology in Toronto, but became intrigued by the molecular underpinnings of endocrine disorders. I moved to Harvard Medical School and Brigham and Women’s Hospital to pursue basic science research training in the regulation of gonadotropin gene expression under the mentorship of Dr. William Chin in the Genetics Division. My initial research focused on the mechanisms of differential regulation of luteinising hormone and follicle stimulating hormone; more recently, I have moved “further up” the hypothalamic-pituitary-gonadal axis to study the neuroendocrine regulation of GnRH secretion.

What you are most proud of in your career so far?

Scientifically, I’m most proud of our discovery that mutations in a gene known as MKRN3, or Makorin Ring Finger Protein 3, cause central precocious puberty. This was the first major genetic cause of precocious puberty to be identified and is now recognized to explain close to half of all cases of familial central precocious puberty. This discovery has identified the first known inhibitor of human GnRH secretion and has opened up an entirely new field of investigation. It is also important translationally and has highlighted the role of genetic imprinting in the control of human pubertal timing. I’m particularly proud of this accomplishment because of its collaborative and multidisciplinary nature – it has involved an international network of collaborators and has helped to launch the careers of several of our trainees.

What are you presenting in your Medal Lecture at SfE BES 2018?

I will be talking about our discovery of the role of MKRN3 in the timing of puberty and the link of loss of function mutations in MKRN3 with central precocious puberty.  In particular, I will expand on the studies we have performed since discovering this link in order to better understand the role and mechanisms of action of MKRN3 in puberty onset.

What are you looking forward to at this year’s conference?

I’m particularly looking forward to seeing my British and other international friends and colleagues, to catch up and hear about their new work, and to discuss ongoing and potential future collaborations. One thing that I would recommend to others is to take maximum advantage of the opportunity to catch up with new advances in their fields and to network with colleagues. It’s a great opportunity to meet new colleagues and make new connections!

What do you think are the biggest challenges in endocrinology right now?

Two of the biggest challenges in endocrinology are addressing the rising rates of obesity and diabetes mellitus. The prevalence of these metabolic disorders is rapidly increasing, not only in developed countries, but also in the developing world. We need more research to better understand the pathogenesis of these metabolic disorders. Interestingly, neuroendocrinology is increasingly recognized to play a key role in metabolic disorders, with neuropeptides and neural circuits playing key roles both in appetite and energy homeostasis, as well as linking metabolism to other areas of physiology such as reproduction and growth.

What do you think will be the next major breakthrough in your field?

I believe that neuroscience is an incredibly exciting area that is poised for major breakthroughs. The combination of advances in human genetics together with advances in our abilities to study the brain are allowing neural circuits to be mapped in detail and are leading to new discoveries in mechanisms underlying neurological and neuroendocrine diseases. I am hopeful that these advances will in turn lead to new treatments for these disorders. Endocrinology is particularly important for our understanding of sex differences in predisposition to and responses to treatments for neurological disorders, such as Alzheimer’s and Parkinson’s disease.

In addition, advances in our understanding of neuroendocrine circuits will lead to new therapies targeting neuroendocrine pathways controlling metabolism and reproduction. The recent discovery that menopausal vasomotor symptoms (i.e., hot flashes) are mediated by the neuropeptide, neurokinin B, and that neurokinin B antagonists can effectively target and reduce the frequency of these vasomotor symptoms, is a great example of such a breakthrough.

What do you enjoy most about your work?

I’m so fortunate to have one of the best jobs in the world! My work is intellectually and socially stimulating. No two days are alike – between teaching students, doing research, and seeing patients, I’m learning new things every day. I have wonderful opportunities to meet and interact with a broad variety of interesting and kind people.

Any words of wisdom for aspiring endocrinologists out there?

Endocrinology is a fantastic field! The diversity of endocrine disorders and the multi-system effects of hormones leads to a very integrative field that is intellectually stimulating and satisfying. There is still so much to be learned and so many research questions to be answered. Furthermore, the endocrine specialty provides the opportunity to have sustained, long-term relationships with patients and to observe the impact of treatment on their health and quality of life.

You can hear Professor Kaiser’s International Medal Lecture, “Puberty: what are the neuroendocrine triggers for the biological end of childhood?” on Monday 19 November, in the Lomond Auditorium at 14:15-14:45. Find out more about the scientific programme for SfE BES 2018.

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