Louis Tartaglia

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Louis Anthony Tartaglia is an American biochemist, pharmaceutical scientist, and entrepreneur. [1] 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. [2] [3] 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. [4] [5] 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, [6] and as a member of several advisory boards, [7] Tartaglia has helped start a number of therapeutics oriented companies that have found their way into the market, among them Agios, [8] Editas, [9] Rhythm, [10] and Zafgen. [11]

Contents

Tartaglia was born in Albany, New York in 1963.

Education

In 1990, Tartaglia received his Ph.D. in biochemistry from UC Berkeley in the laboratory of professor Bruce Ames.  Between 1990 and 1993, he did postdoctoral research in the lab of David Goeddel at Genentech, authoring over 10 original papers in peer-reviewed journals. [12]

Career

In 1993, Tartaglia began his career as the first employee and scientist at Millennium Pharmaceuticals, Inc. He led a lab that cloned and characterized several genes related  to obesity and diabetes, which led to over 30 original scientific publications and over 20 patents. Promoted to Vice President of Metabolic Diseases in 1999, he led a team devoted to discovering drug candidates for the firm's pharmaceutical company partners. In 2004, he became Vice President of New Ventures at Millenium. Between 2004 and 2007, he worked in Gene Logic. In 2007, joined a new venture capital firm (Third Rock Ventures) devoted to  launching new biotech companies.  At this firm, he accompanied the start of companies Agios, Ablexis, Rhythm, Editas, Ember, and Zafgen. In 2016 Tartaglia joined 5AM Ventures to lead their de novo company formation where he oversaw the foundation of companies Entrada and Diagon. [7]

Research

As a Ph.D. student under Bruce Ames at UC Berkeley in 1985, he studied the bacterial defense to oxidants and co-authored half a dozen papers, including an article in Science describing the first known transcription factor to be directly activated by oxidative stress. [13]

During his postdoctoral years at Genentech under David Goeddel, Tartaglia co-authored a dozen papers on TNF (Tumour necrosis factor) receptors, coining the term “Death Domain” to refer to the signaling of programmed cell death; [14] homologous domains were later found in many receptors and signal transduction molecules.

After joining Millennium Pharmaceuticals in 1993, his group soon cloned the receptor for the "obesity hormone" leptin. [15] [16] He published this work in 1995 in an article which was selected in 2004 by Cell among the 16 most “memorable papers” in its 30-year history. [17] Soon after publication in Cell, this discovery was announced on several national press media. [2] [3] [18]

In a collaborative effort with the Whitehead Institute, in 1999, his group identified a small intestinal protein (FA transport protein), which was found to play a key role in the uptake of dietary fat into the body. [19]

Tartaglia´s further research went on to clone and characterize mitochondrial uncoupling genes UCP2 and UCP3, in collaboration with colleagues from Prague and Beaverton, Oregon). [20] [21]

Publications

His most cited original research articles are: [4]

His most cited subject review articles are: [4]

Patents

In the industrial milieu, Tartaglia has been granted over 30 patents involving biomedical methods. These include the leptin receptor patent, [22] the screening of UCPH (UCP2) levels to monitor weight disorders, [23] and the administration of melanocortin 4 receptor (MC4R) agonists to certain patients, [24] an approach currently undergoing phase 3 trials, sponsored by the patent assignee, Rhythm Pharmaceuticals. [25]

Related Research Articles

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

Leptin is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance by inhibiting hunger, which in turn diminishes fat storage in adipocytes. Leptin is coded for by the LEP gene. Leptin acts on cell receptors in the arcuate and ventromedial nuclei, as well as other parts of the hypothalamus and dopaminergic neurons of the ventral tegmental area, consequently mediating feeding.

Tumor necrosis factor Protein

Tumor necrosis factor is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain.

<span class="mw-page-title-main">Richard Axel</span> American molecular biologist

Richard Axel is an American molecular biologist and university professor in the Department of Neuroscience at Columbia University and investigator at the Howard Hughes Medical Institute. His work on the olfactory system won him and Linda Buck, a former postdoctoral research scientist in his group, the Nobel Prize in Physiology or Medicine in 2004.

<span class="mw-page-title-main">Michael Stuart Brown</span> American geneticist and Nobel laureate

Michael Stuart Brown ForMemRS is an American geneticist and Nobel laureate. He was awarded the Nobel Prize in Physiology or Medicine with Joseph L. Goldstein in 1985 for describing the regulation of cholesterol metabolism.

TRAF2 Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.

TRADD

Tumor necrosis factor receptor type 1-associated DEATH domain protein is a protein that in humans is encoded by the TRADD gene.

IKK2 Protein-coding gene in the species Homo sapiens

IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein that in humans is encoded by the IKBKB gene.

<span class="mw-page-title-main">Tumor necrosis factor receptor 1</span> Mammalian protein found in Homo sapiens

Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFα).

Baculoviral IAP repeat-containing protein 2

Baculoviral IAP repeat-containing protein 2 is a protein that in humans is encoded by the BIRC2 gene.

TRAF1

TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.

Caspase 10 Protein-coding gene in the species Homo sapiens

Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene.

Leptin receptor 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.

TRAF3 Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene.

Hypocretin (orexin) receptor 2 Protein-coding gene in the species Homo sapiens

Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene.

EPH receptor B4 Protein-coding gene in the species Homo sapiens

Ephrin type-B receptor 4 is a protein that in humans is encoded by the EPHB4 gene.

MAP3K14

Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the MAP3K14 gene.

<span class="mw-page-title-main">Tumor necrosis factor receptor 2</span>

Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) and CD120b, is one of two membrane receptors that binds tumor necrosis factor-alpha (TNFα). Like its counterpart, tumor necrosis factor receptor 1 (TNFR1), the extracellular region of TNFR2 consists of four cysteine-rich domains which allow for binding to TNFα. TNFR1 and TNFR2 possess different functions when bound to TNFα due to differences in their intracellular structures, such as TNFR2 lacking a death domain (DD).

Adipogenesis

Adipogenesis is the formation of adipocytes from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipocytes which lose the potential to differentiate to other types of cells such as chondrocytes, myocytes, and osteoblasts. Terminal differentiation is that preadipocytes differentiate into mature adipocytes. Adipocytes can arise either from preadipocytes resident in adipose tissue, or from bone-marrow derived progenitor cells that migrate to adipose tissue.

Jeffrey Flier American physician

JeffreyFlier is an American physician, endocrinologist, widely cited scientist, Higginson Professor of Medicine and Physiology, and Harvard University Distinguished Service Professor at Harvard Medical School. He was the 21st Dean of the Faculty of Medicine at Harvard University from 2007 to 2016.

Rudolph Leibel

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.

References

  1. ↑ "Student Vision". www.studentvision.org. Retrieved 2020-09-10.
  2. 1 2 "Scientists Report Finding Weight-Control Receptors : Research: Molecular 'antenna' conveys message from protein telling the body to stop eating. Its discovery may lead to treatments for obesity". Los Angeles Times. 1995-12-29. Retrieved 2020-09-29.
  3. 1 2 "A Protein Tells Eaters to Stop". The New York Times. 1996-01-04. ISSN   0362-4331 . Retrieved 2020-09-29.
  4. 1 2 3 "Louis A. Tartaglia - Google Académico". scholar.google.es. Retrieved 2020-08-30.
  5. ↑ "Scopus preview - Scopus - Author details (Tartaglia, Louis A.)". www.scopus.com. Retrieved 2020-08-30.
  6. ↑ Kirsner, Scott. "Some venture firms find both ideas and the money". bostonglobe.com. Retrieved 6 September 2020.
  7. 1 2 "Lou Tartaglia, 5am Ventures: Profile and Biography". Bloomberg.com. Retrieved 2020-09-09.
  8. ↑ "Agios Pharmaceuticals Registration". investor.agios.com. Retrieved 9 September 2020.
  9. ↑ Trafton, Anne (2013-11-25). "Editas Medicine to develop new class of genome editing therapeutics". MIT McGovern Institute. Retrieved 2020-08-30.
  10. ↑ EquityNet. "Rhythm Pharmaceuticals". EquityNet. Retrieved 2020-11-03.
  11. ↑ "Zafgen Inc. Appoints Industry Veteran and Recognized Metabolic Disorders Expert Thomas Hughes, Ph.D., as Company's First Chief Executive Officer - Larimar Therapeutics, Inc". ir.zafgen.com. Retrieved 2020-09-08.
  12. ↑ "Google Scholar". scholar.google.es. Retrieved 2020-11-03.
  13. ↑ G, Storz; La, Tartaglia; Bn, Ames (1990-04-13). "Transcriptional regulator of oxidative stress-inducible genes: direct activation by oxidation". Science. 248 (4952): 189–94. Bibcode:1990Sci...248..189S. doi:10.1126/science.2183352. PMID   2183352.
  14. ↑ La, Tartaglia; Tm, Ayres; Gh, Wong; Dv, Goeddel (1993-09-10). "A novel domain within the 55 kd TNF receptor signals cell death". Cell. 74 (5): 845–53. doi:10.1016/0092-8674(93)90464-2. PMID   8397073. S2CID   38732043.
  15. ↑ Tartaglia, L. A.; Dembski, M.; Weng, X.; Deng, N.; Culpepper, J.; Devos, R.; Richards, G. J.; Campfield, L. A.; Clark, F. T.; Deeds, J.; Muir, C. (1995-12-29). "Identification and expression cloning of a leptin receptor, OB-R". Cell. 83 (7): 1263–1271. doi: 10.1016/0092-8674(95)90151-5 . ISSN   0092-8674. PMID   8548812. S2CID   6534085.
  16. ↑ "Overcoming Leptin Resistance In The Battle Against Obesity". www.medicalnewstoday.com. 2015-07-08. Retrieved 2020-09-10.
  17. ↑ "A Tribute to Exciting Biology". Cell. 116 (2): 141. 2004. doi: 10.1016/S0092-8674(04)00056-X . S2CID   9612194.
  18. ↑ Weiss, Rick (1995-12-29). "RESEARCHERS TRACK DOWN RECEPTORS THAT TELL BRAIN TO STOP EATING'". Washington Post. ISSN   0190-8286 . Retrieved 2020-11-03.
  19. ↑ Stahl, A.; Hirsch, D. J.; Gimeno, R. E.; Punreddy, S.; Ge, P.; Watson, N.; Patel, S.; Kotler, M.; Raimondi, A.; Tartaglia, L. A.; Lodish, H. F. (1999). "Identification of the major intestinal fatty acid transport protein". Molecular Cell. 4 (3): 299–308. doi: 10.1016/s1097-2765(00)80332-9 . ISSN   1097-2765. PMID   10518211.
  20. ↑ Jezek, P.; Zácková, M.; Reháková, Z.; Růzicka, M.; Borecký, J.; Skobisová, E.; Brucknerová, J.; Garlid, K. D.; Gimeno, R. E.; Tartaglia, L. A. (1999-07-16). "Existence of uncoupling protein-2 antigen in isolated mitochondria from various tissues". FEBS Letters. 455 (1–2): 79–82. doi: 10.1016/s0014-5793(99)00853-4 . ISSN   0014-5793. PMID   10428476. S2CID   7207485.
  21. ↑ Jabůrek, M.; Varecha, M.; Gimeno, R. E.; Dembski, M.; Jezek, P.; Zhang, M.; Burn, P.; Tartaglia, L. A.; Garlid, K. D. (1999-09-10). "Transport function and regulation of mitochondrial uncoupling proteins 2 and 3". The Journal of Biological Chemistry. 274 (37): 26003–26007. doi: 10.1074/jbc.274.37.26003 . ISSN   0021-9258. PMID   10473545. S2CID   28476624.
  22. ↑ "Millennium Issued Broad Patent Relating to the Leptin Receptor and Body Weight Regulation". www.takedaoncology.com. Retrieved 2020-09-10.
  23. ↑ "Millennium Issued Patent For Weight Disorder Treatment". www.drugdiscoveryonline.com. Retrieved 2020-09-10.
  24. ↑ "Method of treating melanocortin-4 receptor-associated disorders in heterozygous carriers". pubchem.ncbi.nlm.nih.gov. Retrieved 10 September 2020.
  25. ↑ "Rhythm Pharmaceuticals Announces Late-breaking Data from Phase 3 Trials of Setmelanotide in POMC and LEPR Deficiency Obesities at ObesityWeek 2019 | Rhythm Pharmaceuticals, Inc". ir.rhythmtx.com. Retrieved 2020-09-10.
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