Louis Tartaglia Explained

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]

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.

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.^[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:

• Tartaglia, L.A., Ayres, T.M., Wong, G.H. and Goeddel, D.V., (1993). A novel domain within the 55 kd TNF receptor signals cell death. Cell, 74(5), pp.845-853. According to Google Scholar, this article has been cited 1657 times.
• L A Tartaglia 1, M Dembski, X Weng, N Deng, J Culpepper, R Devos, G J Richards, L A Campfield, F T Clark, J Deeds, C Muir, S Sanker, A Moriarty, K J Moore, J S Smutko, G G Mays, E A Wool, C A Monroe, R I Tepper. (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83(7):1263-71. According to Google Scholar, this article has been cited 4548 times.
• Chen, H., Charlat, O., Tartaglia, L.A., Woolf, E.A., Weng, X., Ellis, S.J., Lakey, N.D., Culpepper, J., More, K.J., Breitbart, R.E. and Duyk, G.M., (1996). Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell, 84(3), pp.491-495. According to Google Scholar, this article has been cited 2512 times.
• Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. The Journal of Clinical Investigation 112.12 (2003): 1821-1830. According to Google Scholar, this article has been cited 6809 times.

His most cited subject review articles are:

• Tartaglia, L.A. and Goeddel, D.V., (1992). Two TNF receptors. Immunology today, 13(5), pp.151-153. According to Google Scholar, this article has been cited 1338 times.
• Tartaglia, L.A., (1997). The leptin receptor. Journal of Biological Chemistry, 272(10), pp.6093-6096. According to Google Scholar, this article has been cited 1744 times.

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]

Notes and References

1. Web site: Student Vision. 2020-09-10. www.studentvision.org.
2. Web site: 1995-12-29. 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.. 2020-09-29. Los Angeles Times. en-US.
3. News: 1996-01-04. A Protein Tells Eaters to Stop. en-US. The New York Times. 2020-09-29. 0362-4331.
4. Web site: Louis A. Tartaglia - Google Académico. 2020-08-30. scholar.google.es.
5. Web site: Scopus preview - Scopus - Author details (Tartaglia, Louis A.). 2020-08-30. www.scopus.com.
6. Web site: Kirsner. Scott. Some venture firms find both ideas and the money. 6 September 2020. bostonglobe.com. Globe Correspondent,June 17, 2012.
7. Web site: Lou Tartaglia, 5am Ventures: Profile and Biography. 2020-09-09. Bloomberg.com. en.
8. Web site: Agios Pharmaceuticals Registration . investor.agios.com . 9 September 2020.
9. Web site: Trafton. Anne. 2013-11-25. Editas Medicine to develop new class of genome editing therapeutics. 2020-08-30. MIT McGovern Institute. en-US.
10. Web site: EquityNet. Rhythm Pharmaceuticals. 2020-11-03. EquityNet.
11. Web site: Zafgen Inc. Appoints Industry Veteran and Recognized Metabolic Disorders Expert Thomas Hughes, Ph.D., as Company's First Chief Executive Officer - Larimar Therapeutics, Inc.. 2020-09-08. ir.zafgen.com. en.
12. Web site: Google Scholar. 2020-11-03. scholar.google.es.
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. 10.1126/science.2183352. en. 2183352. 1990Sci...248..189S.
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. 10.1016/0092-8674(93)90464-2. en. 8397073. 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. 10.1016/0092-8674(95)90151-5. 0092-8674. 8548812. 6534085. free.
16. Web site: 2015-07-08. Overcoming Leptin Resistance In The Battle Against Obesity. 2020-09-10. www.medicalnewstoday.com. en.
17. 2004. A Tribute to Exciting Biology. Cell. en. 116. 2. 141. 10.1016/S0092-8674(04)00056-X. 9612194. free.
18. News: Weiss. Rick. 1995-12-29. RESEARCHERS TRACK DOWN RECEPTORS THAT TELL BRAIN TO STOP EATING'. en-US. Washington Post. 2020-11-03. 0190-8286.
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. 10.1016/s1097-2765(00)80332-9. 1097-2765. 10518211. free.
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. 10.1016/s0014-5793(99)00853-4. 0014-5793. 10428476. 7207485. free.
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. 10.1074/jbc.274.37.26003. 0021-9258. 10473545. 28476624. free.
22. Web site: Millennium Issued Broad Patent Relating to the Leptin Receptor and Body Weight Regulation. 2020-09-10. www.takedaoncology.com.
23. Web site: Millennium Issued Patent For Weight Disorder Treatment. 2020-09-10. www.drugdiscoveryonline.com.
24. Web site: Method of treating melanocortin-4 receptor-associated disorders in heterozygous carriers . pubchem.ncbi.nlm.nih.gov . 10 September 2020.
25. Web site: Rhythm Pharmaceuticals Announces Late-breaking Data from Phase 3 Trials of Setmelanotide in POMC and LEPR Deficiency Obesities at ObesityWeek 2019 Rhythm Pharmaceuticals, Inc.. 2020-09-10. ir.rhythmtx.com. en.