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]

Tartaglia was born in Albany, New York in 1963.

Education[edit]

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[edit]

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[edit]

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[edit]

His most cited original research articles are:[4]

  • 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:[4]

  • 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[edit]

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]

References[edit]

  1. ^ "Student Vision". www.studentvision.org. Retrieved 2020-09-10.
  2. ^ a b "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. ^ a b "A Protein Tells Eaters to Stop". The New York Times. 1996-01-04. ISSN 0362-4331. Retrieved 2020-09-29.
  4. ^ a b c "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. ^ a b "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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