William G. Kaelin Jr. (born November 23, 1957) is an American Nobel Laureate
physician-scientist A physician-scientist is traditionally a holder of a medical degree and a doctor of philosophy also known as an MD-PhD. Compared to other clinicians, physician-scientists invest significant time and professional effort in scientific research and ...
. He is a professor of medicine at
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
and the
Dana–Farber Cancer Institute
Dana–Farber Cancer Institute is a comprehensive cancer treatment and research institution in Boston, Massachusetts. Dana–Farber is the founding member of Dana–Farber/Harvard Cancer Center, Harvard's Comprehensive Cancer Center designated b ...
. His laboratory studies
tumor suppressor
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...
proteins.
In 2016, Kaelin received the
Albert Lasker Award for Basic Medical Research
The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 5 ...
and the
AACR Princess Takamatsu Award.
He also won the
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 ...
in 2019 along with
Peter J. Ratcliffe and
Gregg L. Semenza
Gregg Leonard Semenza (born July 12, 1956) is a Pediatrician and Professor of Genetic Medicine at the Johns Hopkins School of Medicine. He serves as the director of the vascular program at the Institute for Cell Engineering. He is a 2016 recipi ...
.
Early life and education
Kaelin was born in
New York City
New York, often called New York City or NYC, is the List of United States cities by population, most populous city in the United States. With a 2020 population of 8,804,190 distributed over , New York City is also the L ...
on November 23, 1957.
Kaelin earned his bachelor's degree in mathematics and chemistry at
Duke University
Duke University is a private research university in Durham, North Carolina. Founded by Methodists and Quakers in the present-day city of Trinity in 1838, the school moved to Durham in 1892. In 1924, tobacco and electric power industrialist James ...
, and stayed to attain an MD, graduating in 1982. He did his residency in internal medicine at
Johns Hopkins School of Medicine
The Johns Hopkins University School of Medicine (JHUSOM) is the medical school of Johns Hopkins University, a private research university in Baltimore, Maryland. Founded in 1893, the School of Medicine shares a campus with the Johns Hopkins Hospi ...
and his fellowship in oncology at
Dana–Farber Cancer Institute
Dana–Farber Cancer Institute is a comprehensive cancer treatment and research institution in Boston, Massachusetts. Dana–Farber is the founding member of Dana–Farber/Harvard Cancer Center, Harvard's Comprehensive Cancer Center designated b ...
(DFCI). After deciding as an undergraduate that research was not a strength of his, at DFCI he did research in the lab of
David Livingston
David Livingston is an American television producer and director. He is mostly known for his involvement in the writing and production of the various modern ''Star Trek'' franchises.
Livingston also has production credits on several episodes ...
, where he found success in the study of
retinoblastoma
Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively fo ...
.
In 1992, he set up his own lab at DFCI down the hall from Livingston's where he investigated hereditary forms of cancer such as
von Hippel–Lindau disease
Von Hippel–Lindau disease (VHL), also known as Von Hippel–Lindau syndrome, is a rare genetic disorder with multisystem involvement. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation ...
. He became a professor at
Harvard Medical School
Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
in 2002.
Career
He became Assistant Director of Basic Science at the Dana–Farber/Harvard Cancer Center in 2008. His research at Dana–Farber has focused on understanding the role of mutations in tumor suppressor genes in cancer development. His major work has been on the
retinoblastoma
Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively fo ...
, von Hippel–Lindau, and
p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
tumor suppressor genes.
His work has been funded by the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
,
American Cancer Society
The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
,
Doris Duke Charitable Foundation
Doris Duke (November 22, 1912 – October 28, 1993) was an American billionaire tobacco heiress, philanthropist, art collector, horticulturalist, and socialite. She was often called "the richest girl in the world". Her great wealth, luxurious l ...
and others.
He serves as Vice-Chair of Scientific Programs on th
Damon Runyon Cancer Research Foundation Boardof Directors and Chair of the Damon Runyon Physician-Scientist Training Award selection committee and is a member of the board of directors at
Eli Lilly
Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and r ...
and the
Stand Up to Cancer
Stand Up to Cancer (SU2C) is a charitable program of the Entertainment Industry Foundation (EIF). SU2C aims to raise significant funds for translational cancer research through online and televised efforts. Central to the program is a telethon tha ...
scientific advisory committee.
Research
![HIF Nobel Prize Physiology Medicine 2019 Hegasy ENG](https://upload.wikimedia.org/wikipedia/commons/5/5b/HIF_Nobel_Prize_Physiology_Medicine_2019_Hegasy_ENG.png)
Following his post-doctorate, Kaelin set up a laboratory at Dana-Farber in 1993 to continue his research on tumor suppression. He had become interested in
Von Hippel–Lindau disease
Von Hippel–Lindau disease (VHL), also known as Von Hippel–Lindau syndrome, is a rare genetic disorder with multisystem involvement. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation ...
(VHL). VHL tumors, caused by gene mutation, were known to be
angiogenic
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splittin ...
, creating blood vessels that secreted
erythropoietin
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bo ...
(EPO), a hormone known to be part of the body's mechanic to react to
hypoxia
Hypoxia means a lower than normal level of oxygen, and may refer to:
Reduced or insufficient oxygen
* Hypoxia (environmental), abnormally low oxygen content of the specific environment
* Hypoxia (medical), abnormally low level of oxygen in the tis ...
, or low oxygen levels in the blood. Kaelin hypothesized that there may be a connection between the formation of VHL tumors and the deficiency of the body to detect oxygen.
Kaelin's research found that in VHL subjects, there were genes expressed the formation of a protein critical in the EPO process, but which the mutation suppressed. Kaelin's work aligned with that of
Peter J. Ratcliffe and
Gregg Semenza who separately had identified a two-part protein,
hypoxia-inducible factors
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or Hypoxia (medical), hypoxia. They are only present in ParaHoxozoa, parahoxozoan animals.
Discovery
The ...
(HIF) that was essential to EPO production and which was triggered by oxygen levels in the blood. Kaelin's work found that the VHL protein would help regulate the HIF, and in subjects where the VHL proteins were not present, the HIF would overproduce EPO and lead to cancer.
The combined work of Kaelin, Ratcliffe, and Semenza identified the pathway of how cells detect and react to oxygen levels in the blood, and have led to the development of drugs to help patients with
anaemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
and
kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
.
Personal life
He was married to breast cancer surgeon
Carolyn Kaelin from 1988 until her death from
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...
in 2015. They have two children.
Selected awards
References
External links
* including the Nobel Lecture 7 December 2019 ''The von Hippel-Lindau Tumor Suppressor Protein: Insights into Oxygen Sensing''
{{DEFAULTSORT:Kaelin, William Jr.
1957 births
Living people
Physicians from New York City
Scientists from New York City
Cancer researchers
American Nobel laureates
Nobel laureates in Physiology or Medicine
Duke University School of Medicine alumni
Fellows of the AACR Academy
Harvard Medical School faculty
Recipients of the Albert Lasker Award for Basic Medical Research
Members of the National Academy of Medicine