Holly Ann Ingraham (born 1952) is an American physiologist who is the Herzstein Professor of Molecular Physiology at the

University of California, San Francisco The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It cond ...

. She studies women's health, in particular, sex-dependent central regulation of female metabolism and physiology. She was Elected to the

American Association for the Advancement of Science The American Association for the Advancement of Science (AAAS) is an American international non-profit organization with the stated goals of promoting cooperation among scientists, defending scientific freedom, encouraging scientific respons ...

in 2012, the

American Academy of Arts and Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and ...

in 2019, and the

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...

in 2021.

Early life and education

Ingraham grew up in

Northern California Northern California (colloquially known as NorCal) is a geographic and cultural region that generally comprises the northern portion of the U.S. state of California. Spanning the state's northernmost 48 counties, its main population centers incl ...

. As a child she was gifted a Bausch & Lomb microscope and spent her spare time investigating all the objects she could find close to her home. She started her scientific career as an undergraduate student at the

University of California, San Diego The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Insti ...

(UCSD), where she majored in biology and psychology. Ingraham earned her doctorate at UCSD.

Research and career

Ingraham studies hormone-responsive nodes in the brain. In particular, she is interested in

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

's signalling in the brain and how this impacts female metabolism. She has studied the influence of estrogen-sensitive brain cells on bone density. Over two million people suffer from

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

, with post-menopausal women being particularly vulnerable to the condition. The declining levels of estrogen after menopause can cause bones to become increasingly porous and fragile. Ingraham manipulated neurons in the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

, and found that genetically deleting the estrogen receptor caused female animals to gain weight and become less active. She identified that these heavier mice had increases in bone density of up to 800%. Together with her collaborators, Ingraham investigated estrogen-sensitive brain cells in the

arcuate nucleus The arcuate nucleus of the hypothalamus (also known as ARH, ARC, or infundibular nucleus) is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several ...

, and proposed that estrogen typically signals these neurons to slow bone growth. By deleting these receptors, Ingraham showed that it was possible to reduce this shift. The same was not true in male mice, where manipulating the estrogen signalling had no impact. In female mice that were already suffering from osteoporosis, Ingraham showed that bone density could increase by around 50% in a few weeks. Ingraham has investigated other estrogen-sensitive neurons outside the hypothalamus and how declining health is associated with the depletion of hormones. Ingraham is interested in the development of the

ventromedial nucleus of the hypothalamus The ventromedial nucleus of the hypothalamus (VMN, also sometimes referred to as the ventromedial hypothalamus, VMH) is a nucleus of the hypothalamus. "The ventromedial hypothalamus (VMH) is a distinct morphological nucleus involved in terminatin ...

, the neuroendocrine centre of the brain. She identified that the

herbicide Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page fo ...

atrazine Atrazine is a chlorinated herbicide of the triazine class. It is used to prevent pre-emergence broadleaf weeds in crops such as maize (corn), soybean and sugarcane and on turf, such as golf courses and residential lawns. Atrazine's primary manufa ...

can activate gene networks. Beyond the brain, Ingraham has studied sex-specific differences in gut-brain signalling pathways, in an effort to understand why women are more susceptible to intestinal visceral pain syndromes. Another primary focus of Ingraham's academic activities is directed towards the most vulnerable population in our nation's biomedical educational pipeline – women and minority postdoctoral fellows. As such, she serves as the Director of th
NIGMS-IRACDA Program at UCSF
which provides a cohort of 15-20 scholars with individualized mentoring and career development plans for future success at R1 and R3 institutions.

Awards and honors

* 2002 Brook Byers Basic Science Award * 2006 Herzstein Distinguished Investigator in Molecular Physiology * 2012 Elected to the

* 2017 Chancellor's Award Martin Luther King, Jr. Leadership Award * 2018 Joseph Larner Memorial Lecture in Pharmacology * 2019 Elected to the

* 2021 Elected to the

Personal life

Ingraham is married to David Julius, Professor and Chair of Physiology at UCSF and winner of 2021

Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...

. She and David Julius have a son.

Selected publications

* * *

References

{{DEFAULTSORT:Ingraham, Holly Ann Living people University of California, San Francisco alumni American physiologists Fellows of the American Association for the Advancement of Science Members of the United States National Academy of Sciences University of California, San Francisco faculty 21st-century American women scientists Women physiologists 1952 births