Douglas L. Coleman

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Douglas L. Coleman
Born
Douglas Leonard Coleman [1]

(1931-10-06)October 6, 1931
Stratford, Ontario
Canada [2]
DiedApril 16, 2014(2014-04-16) (aged 82)
Lamoine, Maine
United States [2]
Education McMaster University (BSc)
University of Wisconsin–Madison (PhD)
Known forPrediction of the existence of leptin
Spouse
Beverly J. Benallick
​
​
(died 2009)​
Children3
Awards Canada Gairdner International Award
Shaw Prize in Life science and Medicine
Albert Lasker Award for Basic Medical Research
BBVA Foundation Frontiers of Knowledge Award
King Faisal International Prize in Medicine
Scientific career
Fields Physiology
Biochemistry
Institutions Jackson Laboratory
Thesis Studies on the saturation of sterols by intestinal bacteria  (1958)
Doctoral advisor Carl August Baumann

Douglas L. Coleman (October 6, 1931 - April 16, 2014) was a scientist and professor emeritus at the Jackson Laboratory, in Bar Harbor, Maine. His work predicted that there exists a hormone that can cause mice to feel full, and that a mutation in the gene encoding this hormone can lead to obesity. [3] The gene and corresponding hormone were discovered about 20 years later by Jeffrey M. Friedman, Rudolph Leibel, and their research teams at Rockefeller University, which Friedman named leptin. [4]

Contents

Early life and education

Coleman was born in Stratford, Ontario, Canada in 1931. He was the first in his family to finish high school. [5] He obtained his BSc from McMaster University in 1954. At the encouragement of a biochemistry professor at McMaster, [3] Coleman attended the University of Wisconsin–Madison for a PhD, which he obtained in 1958.

Career

After receiving his PhD, Coleman did not continue in academia or entered the industry, as was common at the time. Instead, he became an associate staff scientist at the Roscoe B. Jackson Memorial Laboratory (now Jackson Laboratory) in Bar Harbor, Maine. [6] Initially planning to stay one to two years, Coleman ended up spending his entire career at the Jackson Laboratory. [7]

He was promoted to a staff scientist at Jackson Laboratory in 1961 and became a senior staff scientist in 1968. He was the assistant director of research from 1968 to 1970 and interim director between 1975 and 1976. [2]

Coleman retired in 1991 [7] at the age of 62. [8]

Research

Before Coleman's experiments, there was evidence that the hypothalamus was a master regulator of energy balance by responding to a factor that traveled in blood. [4] [9] When Coleman joined the Jackson Laboratory, only one obese mouse strain existed. This strain contained a mutation, called ob (for obese), at both copies of the DNA at chromosome 6, and so was designated ob/ob. [3]

In 1966, Coleman and his colleagues reported a second obese mouse strain that looked very similar to ob/ob mice but had another mutation. The mutation occurred in chromosome 4 and was called db (for diabetes). [10] A major difference between the two strains was that the db/db mice had severe diabetes while the ob/ob mice only mild diabetes. Importantly, only mice that were homozygous with the ob or db mutation (meaning they had the mutation at both copies of the DNA) were obese. This meant in these two strains, obesity was an autosomal recessive trait.

Coleman wondered if there existed a biological molecule that caused obesity and was produced in a db/db but not normal mice, or, conversely, if there existed a molecule that prevented obesity in normal mice. Aware of previous parabiosis experiments by William Hervey from the University of Cambridge, who surgically joined the blood vessels of normal rats with rats that had injuries at the hypothalamus, Coleman performed similar experiments on normal, ob/ob and db/db mice. He first joined db/db mice to normal ones, and found that normal mice dramatically ate less, had a large decrease in plasma glucose and insulin levels, and eventually died, while db/db mice were unaffected and kept gaining fat and weight. [11]

He then joined ob/ob mice with normal mice, and observed a completely different scenario: normal mice had no changes but ob/ob mice ate less and lost weight. When Coleman ended the union, ob/ob mice gained weight and became obese again. Lastly, when ob/ob and db/db mice were surgically joined together, db/db mice kept gaining weight whereas ob/ob mice significantly reduced their food intake and weight and died. [12]

His findings led Coleman to conclude that ob/ob mice lacked a circulating factor that regulates food intake and weight, and that db/db mice overproduced this factor but could not respond to it. When db/db mice was joined to ob/ob or normal mice, however, this factor traveled through blood to the other mouse and reduced their eating and weight. [13] Connecting these results to contemporary understanding, he also hypothesized that the hypothalamus contained the area that responded to the circulating factor.

About 20 years later, the genes where ob and db mutations occurred were identified by Jeffrey M. Friedman, Rudolph Leibel (both from Rockefeller University) and Louis Tartaglia (from Millennium Pharmaceuticals, now acquired by Takeda Pharmaceutical Company and renamed Takeda Oncology). [4] The ob gene is now known as LEP and the protein hormone it encodes leptin, a name that Friedman coined. The db gene has been confirmed to be a receptor for the leptin protein, and was renamed LEPR. [14]

Personal life, philanthropy, and death

Coleman met his wife, Beverly J. Benallick, during his undergraduate years at McMaster University, where Benallick was the only female chemistry major at the time. [5] Benallick passed away in 2009. [15]

After retirement, Coleman was involved in forest management, land protection, and nature conservation. He created recreational trails in his 20-hectare woodland for the public and especially students, and also helped his wife found a wildlife garden for people not able to walk the woodland. He was a director and president of the Frenchman Bay Conservancy, and a longtime member of the Lamoine Planning Board. [2]

He established two USD $100,000 funds at the Jackson Laboratory: the Douglas Coleman Research Fund to support early-career scientists studying obesity and diabetes, and the Beverly Coleman Memorial Fund to support young students and educational programmes. [2]

Coleman died in Lamoine, Maine on April 16, 2014. [16] [17]

Honors and awards

Related Research Articles

Insulin resistance (IR) is a pathological condition in which cells either fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.

<span class="mw-page-title-main">Leptin</span> Hormone that inhibits hunger

Leptin is a protein hormone predominantly made by adipocytes and its primary role is likely to regulate long-term energy balance.

A maternal effect is a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother. In genetics, maternal effects occur when an organism shows the phenotype expected from the genotype of the mother, irrespective of its own genotype, often due to the mother supplying messenger RNA or proteins to the egg. Maternal effects can also be caused by the maternal environment independent of genotype, sometimes controlling the size, sex, or behaviour of the offspring. These adaptive maternal effects lead to phenotypes of offspring that increase their fitness. Further, it introduces the concept of phenotypic plasticity, an important evolutionary concept. It has been proposed that maternal effects are important for the evolution of adaptive responses to environmental heterogeneity.

<span class="mw-page-title-main">Adipose tissue</span> Loose connective tissue composed mostly by adipocytes

Adipose tissue (also known as body fat, or simply fat) is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction(SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Adipose tissue is derived from preadipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body. Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as leptin, estrogen, resistin, and cytokines (especially TNFα). In obesity, adipose tissue is also implicated in the chronic release of pro-inflammatory markers known as adipokines, which are responsible for the development of metabolic syndrome, a constellation of diseases, including type 2 diabetes, cardiovascular disease and atherosclerosis. The two types of adipose tissue are white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which generates body heat. The formation of adipose tissue appears to be controlled in part by the adipose gene. Adipose tissue – more specifically brown adipose tissue – was first identified by the Swiss naturalist Conrad Gessner in 1551.

<span class="mw-page-title-main">Adiponectin</span> Mammalian protein found in Homo sapiens

Adiponectin is a protein hormone and adipokine, which is involved in regulating glucose levels and fatty acid breakdown. In humans, it is encoded by the ADIPOQ gene and is produced primarily in adipose tissue, but also in muscle and even in the brain.

<span class="mw-page-title-main">Resistin</span> Mammalian protein found in Homo sapiens

Resistin also known as adipose tissue-specific secretory factor (ADSF) or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein (XCP1) is a cysteine-rich peptide hormone derived from adipose tissue that in humans is encoded by the RETN gene.

<span class="mw-page-title-main">Amylin</span> Peptide hormone that plays a role in glycemic regulation

Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone. It is co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.

<span class="mw-page-title-main">Laboratory rat</span> Rat used for scientific research

Laboratory rats or lab rats are strains of the subspecies Rattus norvegicus domestica which are bred and kept for scientific research. While less commonly used for research than laboratory mice, rats have served as an important animal model for research in psychology and biomedical science.

<span class="mw-page-title-main">Jackson Laboratory</span> Biomedical research institution

The Jackson Laboratory is an independent, non-profit biomedical research institution which was founded by Clarence Cook Little in 1929. It employs over 3,000 employees in Bar Harbor, Maine; Sacramento, California; Farmington, Connecticut; Shanghai, China; and Yokohama, Japan. The institution is a National Cancer Institute-designated Cancer Center and has NIH Centers of Excellence in aging and systems genetics. The stated mission of The Jackson Laboratory is "to discover the genetic basis for preventing, treating and curing human diseases, and to enable research and education for the global biomedical community."

<span class="mw-page-title-main">Agouti-signaling protein</span> Protein-coding gene in the species Homo sapiens

Agouti-signaling protein is a protein that in humans is encoded by the ASIP gene. It is responsible for the distribution of melanin pigment in mammals. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte produces phaeomelanin, or eumelanin. This interaction is responsible for making distinct light and dark bands in the hairs of animals such as the agouti, which the gene is named after. In other species such as horses, agouti signalling is responsible for determining which parts of the body will be red or black. Mice with wildtype agouti will be grey, with each hair being partly yellow and partly black. Loss of function mutations in mice and other species cause black fur coloration, while mutations causing expression throughout the whole body in mice cause yellow fur and obesity.

<span class="mw-page-title-main">Jeffrey M. Friedman</span>

Jeffrey M. Friedman is a molecular geneticist at New York City's Rockefeller University and an Investigator of the Howard Hughes Medical Institute. His discovery of the hormone leptin and its role in regulating body weight has had a major role in the area of human obesity. Friedman is a physician scientist studying the genetic mechanisms that regulate body weight. His research on various aspects of obesity received national attention in late 1994, when it was announced that he and his colleagues had isolated the mouse ob gene and its human homologue. They subsequently found that injections of the encoded protein, leptin, decreases body weight of mice by reducing food intake and increasing energy expenditure. Current research is aimed at understanding the genetic basis of obesity in human and the mechanisms by which leptin transmits its weight-reducing signal.

<span class="mw-page-title-main">Leptin receptor</span> Type I cytokine receptor

Leptin receptor, also known as LEP-R or OB-R, is a type I cytokine receptor, a protein that in humans is encoded by the LEPR gene. LEP-R functions as a receptor for the fat cell-specific hormone leptin. LEP-R has also been designated as CD295. Its location is the cell membrane, and it has extracellular, trans-membrane and intracellular sections.

ob/ob mouse

The ob/ob or obese mouse is a mutant mouse that eats excessively due to mutations in the gene responsible for the production of leptin and becomes profoundly obese. It is an animal model of type II diabetes. Identification of the gene mutated in ob led to the discovery of the hormone leptin, which is important in the control of appetite.

Adipose tissue is an endocrine organ that secretes numerous protein hormones, including leptin, adiponectin, and resistin. These hormones generally influence energy metabolism, which is of great interest to the understanding and treatment of type 2 diabetes and obesity.

Parabiosis is a laboratory technique used in physiological research, derived from the Greek word meaning "living beside." The technique involves the surgical joining of two living organisms in such a way that they develop a single, shared physiological system. Through this unique approach, researchers can study the exchange of blood, hormones, and other substances between the two organisms, allowing for the examination of a wide range of physiological phenomena and interactions. Parabiosis has been employed in various fields of study, including stem cell research, endocrinology, aging research, and immunology.

<span class="mw-page-title-main">Rudolph Leibel</span>

Rudolph Leibel is the Christopher J. Murphy Professor of Diabetes Research, Professor of Pediatrics and Medicine at Columbia University Medical Center, and Director of the Division of Molecular Genetics in the Department of Pediatrics. He is also co-director of the Naomi Berrie Diabetes Center and executive director of the Russell and Angelica Berrie Program in Cellular Therapy, Co-director of the New York Obesity Research Center and the Columbia University Diabetes and Endocrinology Research Center.

<span class="mw-page-title-main">Jose F. Caro</span> American physician

José F. Caro is an American physician, scientist, and educator most notable for his research in obesity and diabetes. The Institute for Scientific Information listed him the third most cited investigator in the world in the field of obesity research during the 1991-2000 period for his work on Leptin. Caro is an artist and a signature member of the Pastel Society of America.

<span class="mw-page-title-main">Sadaf Farooqi</span> British consultant physician

Ismaa Sadaf Farooqi is a Wellcome Trust Senior Research fellow in Clinical Science, professor of Metabolism and Medicine at the University of Cambridge and a consultant physician at Addenbrooke's Hospital in Cambridge, UK.

<span class="mw-page-title-main">Pathophysiology of obesity</span>

Pathophysiology of obesity is the study of disordered physiological processes that cause, result from, or are otherwise associated with obesity. A number of possible pathophysiological mechanisms have been identified which may contribute in the development and maintenance of obesity.

Louis Anthony Tartaglia is an American biochemist, pharmaceutical scientist, and entrepreneur. As a scientist, he is known for first identifying and cloning the leptin receptor in 1995, a discovery that prompted immediate coverage in US national media given its expected clinical significance. He is also known for studying signaling mechanisms from the tumor necrosis factor (TNF) receptors, and for publishing studies in the fields of obesity and diabetes which are often discussed in subject reviews. After moving from academia to industry in 1990, for over a decade he accompanied the growth of Millennium Pharmaceuticals, reaching top positions within the company. From executive roles he has occupied in venture capital firms, and as a member of several advisory boards, Tartaglia has helped start a number of therapeutics oriented companies that have found their way into the market, among them Agios, Editas, Rhythm, and Zafgen.

References

  1. ↑ Watts, Geoff (2014). "Douglas Leonard Coleman". The Lancet . 383 (9933): 1966. doi: 10.1016/S0140-6736(14)60946-6 . PMID   24936629. S2CID   39828635. Archived from the original on October 2, 2023. Retrieved October 2, 2023.
  2. 1 2 3 4 5 Peterson, Joyce (April 16, 2014). "Douglas L. Coleman, Ph.D., Jackson Laboratory Professor Emeritus, 1931-2014". Jackson Laboratory. Archived from the original on October 2, 2023. Retrieved October 2, 2023.
  3. 1 2 3 Coleman, Douglas L. (2010). "A historical perspective on leptin" (PDF). Nature Medicine . 16 (10): 1097–1099. doi:10.1038/nm1010-1097. PMID   20930752. S2CID   21890417. Archived from the original (PDF) on October 4, 2023. Retrieved October 4, 2023.
  4. 1 2 3 Flier, Jeffrey S.; Maratos-Flier, Eleftheria (2010). "Lasker lauds leptin". Cell . 143 (1): 9–12. doi: 10.1016/j.cell.2010.09.021 . PMID   20887884.
  5. 1 2 Coleman, Thomas R. (2014). "Douglas L. Coleman, 1931–2014". Diabetologia . 57 (12): 2429–2430. doi: 10.1007/s00125-014-3393-7 . PMC   4218972 . PMID   25287710.
  6. ↑ Neill, Ushma S. (2010). "Leaping for leptin: the 2010 Albert Lasker Basic Medical Research Award goes to Douglas Coleman and Jeffrey M. Friedman". Journal of Clinical Investigation . 120 (10): 3413–3418. doi: 10.1172/JCI45094 . PMC   2947251 .
  7. 1 2 "Autobiography of Douglas L Coleman". Shaw Prize. Archived from the original on October 6, 2023. Retrieved October 6, 2023.
  8. ↑ Friedman, Jeffrey (2014). "Douglas Coleman (1931–2014)". Nature . 509 (7502): 564. Bibcode:2014Natur.509..564F. doi: 10.1038/509564a . PMID   24870535.
  9. ↑ Fève, Bruno; Bastard, Jean-Philippe (2012). "From the conceptual basis to the discovery of leptin". Biochimie . 94 (10): 2065–2068. doi:10.1016/j.biochi.2012.06.028. PMID   22771464 . Retrieved October 11, 2023.
  10. ↑ Hummel, Katharine P.; Dickie, Margaret M.; Coleman, Douglas L. (1966). "Diabetes, a New Mutation in the Mouse". Science . 153 (3740): 1127–1128. Bibcode:1966Sci...153.1127H. doi:10.1126/science.153.3740.1127. PMID   5918576. S2CID   8718770 . Retrieved October 11, 2023.
  11. ↑ Coleman, D. L.; Hummel, K. P. (1969). "Effects of parabiosis of normal with genetically diabetic mice". American Journal of Physiology . 217 (5): 1298–1304. doi:10.1152/ajplegacy.1969.217.5.1298. PMID   5346292 . Retrieved October 12, 2023.
  12. ↑ Coleman, D. L. (1973). "Effects of parabiosis of obese with diabetes and normal mice" (PDF). Diabetologia . 9 (4): 294–298. doi: 10.1007/BF01221857 . PMID   4767369. Archived from the original (PDF) on October 12, 2023. Retrieved October 12, 2023.
  13. ↑ Coleman, D. L. (1978). "Obese and diabetes: Two mutant genes causing diabetes-obesity syndromes in mice" (PDF). Diabetologia. 14 (3): 141–148. doi: 10.1007/BF00429772 . PMID   350680. Archived from the original (PDF) on October 11, 2023. Retrieved October 11, 2023.
  14. ↑ White, David W.; Kuropatwinski, Karen K.; Devos, Rene; Baumann, Heinz; Tartaglia, Louis A. (1997). "Leptin receptor (OB-R) signaling. Cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization". Journal of Biological Chemistry . 272 (7): 4065–4071. doi: 10.1074/jbc.272.7.4065 . PMID   9020115.
  15. ↑ "Beverly Coleman". Bangor Daily News . April 25, 2009. Archived from the original on October 6, 2023. Retrieved October 6, 2023.
  16. ↑ Altman, Lawrence K. (April 25, 2014). "Douglas L. Coleman, 82, Dies; Found a Genetic Cause of Obesity". The New York Times . Archived from the original on October 15, 2023.
  17. ↑ "Douglas L. Coleman". The Ellsworth American . April 17, 2014. Archived from the original on October 15, 2023. Retrieved October 15, 2023.
  18. ↑ "Douglas L. Coleman". National Academy of Sciences. Archived from the original on October 10, 2023. Retrieved October 10, 2023.
  19. ↑ "Douglas Coleman". Gairdner Foundation. Archived from the original on October 10, 2023. Retrieved October 10, 2023.
  20. ↑ "The Prize in Life Science & Medicine 2009". Shaw Prize. Archived from the original on October 10, 2023. Retrieved October 10, 2023.
  21. ↑ "2010 Albert Lasker Basic Medical Research Award". Lasker Award. Archived from the original on October 7, 2023. Retrieved October 7, 2023.
  22. ↑ "Douglas L. Coleman". BBVA Foundation Frontiers of Knowledge Award. Archived from the original on October 14, 2023. Retrieved October 14, 2023.
  23. ↑ "Jackson Laboratory professor emeritus Douglas Coleman wins BBVA, King Faisal awards". EurekAlert! . January 29, 2013. Archived from the original on October 14, 2023. Retrieved October 14, 2023.
  24. ↑ Shypula, Brian (February 11, 2013). "Douglas Coleman's research found biological basis for some forms of obesity in humans". The Beacon Herald . Archived from the original on October 14, 2023. Retrieved October 14, 2023.
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