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Karen Takane

  • ASSISTANT PROFESSOR Medicine, Endocrinology, Diabetes and Bone Disease
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Education

  • Fellowship, University of Texas Southwestern Medical Center at Dallas

  • B.S., University of Michigan

  • University of Texas Southwestern Medical Center at Dallas

Biography


    Dr. Karen Takane has developed and maintains the core facility for adenoviruses encoding PTHrP & its mutants, HGF, cdks, cyclins, and PL1 as well as other growth and differentiation factors for overexpression in rodent and human isolated islets and rodent insulinoma & smooth muscle cells for our lab and others in the division.  She also performs surveillance qPCR on adenovirus preps to prevent wild type adenovirus contamination.

    Dr. Takane has developed adenoviruses expressing cell-cycle factors, such as cdk4, cdk6, cyclin D1, cyclin D3, cyclin E, E2F1, E2F3, & c-myc under the control of a tetracycline-responsive promoter to induce isolated rodent and human islets to proliferate in a controlled manner, and determined the time course and dose responsiveness of tetracycline induction and persistence of expression of cdk6 and cyclin D1 in infected isolated human islets ex vivo.  She has demonstrated that gene expression as well as proliferation can be turned off and back on when Doxycycline is removed or reintroduced ex vivo.  To limit inducible gene expression solely to beta cells, Dr. Takane has characterized an insulin promoter specific tet-transactivator adenovirus. 

Publications

Hersh LB, Takane K, Gylys K, Moomaw C, Slaughter C. Conservation of amino acid sequences between human and porcine choline acetyltransferase. Journal of neurochemistry 1988 Dec; 51(6).

Takane KK, George FW, Wilson JD. Androgen receptor of rat penis is down-regulated by androgen. The American journal of physiology 1990 Jan; 258(1 Pt 1).

Takane KK, Husmann DA, McPhaul MJ, Wilson JD. Androgen receptor levels in the rat penis are controlled differently in distinctive cell types. Endocrinology 1991 May; 128(5).

Takane KK, Wilson JD, McPhaul MJ. Decreased levels of the androgen receptor in the mature rat phallus are associated with decreased levels of androgen receptor messenger ribonucleic acid. Endocrinology 1991 Aug; 129(2).

Takane KK, McPhaul MJ. Functional analysis of the human androgen receptor promoter. Molecular and cellular endocrinology 1996 May; 119(1).

Garcia-Ocaña A, Takane KK, Syed MA, Philbrick WM, Vasavada RC, Stewart AF. Hepatocyte growth factor overexpression in the islet of transgenic mice increases beta cell proliferation, enhances islet mass, and induces mild hypoglycemia. The Journal of biological chemistry 2000 Jan; 275(2).

de Miguel F, Fiaschi-Taesch N, López-Talavera JC, Takane KK, Massfelder T, Helwig JJ, Stewart AF. The C-terminal region of PTHrP, in addition to the nuclear localization signal, is essential for the intracrine stimulation of proliferation in vascular smooth muscle cells. Endocrinology 2001 Sep; 142(9).

García-Ocaña A, Vasavada RC, Cebrian A, Reddy V, Takane KK, López-Talavera JC, Stewart AF. Transgenic overexpression of hepatocyte growth factor in the beta-cell markedly improves islet function and islet transplant outcomes in mice. Diabetes 2001 Dec; 50(12).

Cebrian A, García-Ocaña A, Takane KK, Sipula D, Stewart AF, Vasavada RC. Overexpression of parathyroid hormone-related protein inhibits pancreatic beta-cell death in vivo and in vitro. Diabetes 2002 Oct; 51(10).

Garcia-Ocana A, Takane KK, Reddy VT, Lopez-Talavera JC, Vasavada RC, Stewart AF. Adenovirus-mediated hepatocyte growth factor expression in mouse islets improves pancreatic islet transplant performance and reduces beta cell death. The Journal of biological chemistry 2003 Jan; 278(1).

Lopez-Talavera JC, Garcia-Ocaña A, Sipula I, Takane KK, Cozar-Castellano I, Stewart AF. Hepatocyte growth factor gene therapy for pancreatic islets in diabetes: reducing the minimal islet transplant mass required in a glucocorticoid-free rat model of allogeneic portal vein islet transplantation. Endocrinology 2004 Feb; 145(2).

Cozar-Castellano I, Takane KK, Bottino R, Balamurugan AN, Stewart AF. Induction of beta-cell proliferation and retinoblastoma protein phosphorylation in rat and human islets using adenovirus-mediated transfer of cyclin-dependent kinase-4 and cyclin D1. Diabetes 2004 Jan; 53(1).

Fiaschi-Taesch N, Takane KK, Masters S, Lopez-Talavera JC, Stewart AF. Parathyroid-hormone-related protein as a regulator of pRb and the cell cycle in arterial smooth muscle. Circulation 2004 Jul; 110(2).

Rao P, Roccisana J, Takane KK, Bottino R, Zhao A, Trucco M, García-Ocaña A. Gene transfer of constitutively active Akt markedly improves human islet transplant outcomes in diabetic severe combined immunodeficient mice. Diabetes 2005 Jun; 54(6).

Fiaschi-Taesch N, Sicari BM, Ubriani K, Bigatel T, Takane KK, Cozar-Castellano I, Bisello A, Law B, Stewart AF. Cellular mechanism through which parathyroid hormone-related protein induces proliferation in arterial smooth muscle cells: definition of an arterial smooth muscle PTHrP/p27kip1 pathway. Circulation research 2006 Oct; 99(9).

Fujinaka Y, Takane K, Yamashita H, Vasavada RC. Lactogens promote beta cell survival through JAK2/STAT5 activation and Bcl-XL upregulation. The Journal of biological chemistry 2007 Oct; 282(42).

Vasavada RC, Wang L, Fujinaka Y, Takane KK, Rosa TC, Mellado-Gil JM, Friedman PA, Garcia-Ocaña A. Protein kinase C-zeta activation markedly enhances beta-cell proliferation: an essential role in growth factor mediated beta-cell mitogenesis. Diabetes 2007 Nov; 56(11).

Fiaschi-Taesch NM, Berman-Weinberg D, Sicari BM, Takane KK, Garcia-Ocaña A, Ricordi C, Kenyon NS, Stewart AF. Hepatocyte Growth Factor (HGF) Enhances Engraftment and Function of Non-Human Primate Islets. Diabetes 2008; 57: 2745-54.

Cozar-Castellano I, Harb G, Selk K, Takane K, Vasavada R, Sicari B, Law B, Zhang P, Scott DK, Fiaschi-Taesch N, Stewart AF. Lessons from the first comprehensive molecular characterization of cell cycle control in rodent insulinoma cell lines. Diabetes 2008 Nov; 57(11).

Fiaschi-Taesch N, Sicari B, Ubriani K, Cozar-Castellano I, Takane KK, Stewart AF. Mutant parathyroid hormone-related protein, devoid of the nuclear localization signal, markedly inhibits arterial smooth muscle cell cycle and neointima formation by coordinate up-regulation of p15Ink4b and p27kip1. Endocrinology 2009 Mar; 150(3).

Fiaschi-Taesch N, Bigatel TA, Sicari B, Takane KK, Salim F, Velazquez-Garcia S, Harb G, Selk K, Cozar-Castellano I, Stewart AF. Survey of the human pancreatic beta-cell G1/S proteome reveals a potential therapeutic role for cdk-6 and cyclin D1 in enhancing human beta-cell replication and function in vivo. Diabetes 2009 Apr; 58(4).

González-Pertusa JA, Dubé J, Valle SR, Rosa TC, Takane KK, Mellado-Gil JM, Perdomo G, Vasavada RC, García-Ocaña A. Novel proapoptotic effect of hepatocyte growth factor: synergy with palmitate to cause pancreatic {beta}-cell apoptosis. Endocrinology 2010 Apr; 151(4).

Guthalu Kondegowda N, Joshi-Gokhale S, Harb G, Williams K, Zhang XY, Takane KK, Zhang P, Scott DK, Stewart AF, Garcia-Ocaña A, Vasavada RC. Parathyroid hormone-related protein enhances human ß-cell proliferation and function with associated induction of cyclin-dependent kinase 2 and cyclin E expression. Diabetes 2010 Dec; 59(12).

Blouin CM, Prado C, Takane KK, Lasnier F, Garcia-Ocana A, Ferré P, Dugail I, Hajduch E. Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling. Diabetes 2010 Mar; 59(3).

25. Fiaschi-Taesch NM, Salim F, Kleinberger J, Troxell R, Cozar-Castellano I, Selk K, Cherok E, Takane KK, Stewart AF. Induction of human beta cell proliferation and engraftment using a single G1/S regulatory molecule, cdk6. Diabetes 2010; 59: 1926-36.

Velazquez-Garcia S, Valle S, Rosa TC, Takane KK, Demirci C, Alvarez-Perez JC, Mellado-Gil JM, Ernst S, Scott DK, Vasavada RC, Alonso LC, Garcia-Ocaña A. Activation of protein kinase C-ζ in pancreatic β-cells in vivo improves glucose tolerance and induces β-cell expansion via mTOR activation. Diabetes 2011 Oct; 60(10).

Karslioglu E, Kleinberger JW, Salim FG, Cox AE, Takane KK, Scott DK, Stewart AF. cMyc is a principal upstream driver of beta-cell proliferation in rat insulinoma cell lines and is an effective mediator of human beta-cell replication. Molecular endocrinology (Baltimore, Md.) 2011 Oct; 25(10).

Walpita D, Hasaka T, Spoonamore J, Vetere A, Takane KK, Fomina-Yadlin D, Fiaschi-Taesch N, Shamji A, Clemons PA, Stewart AF, Schreiber SL, Wagner BK. A human islet cell culture system for high-throughput screening. Journal of biomolecular screening 2012 Apr; 17(4).

Takane KK, Kleinberger JW, Salim FG, Fiaschi-Taesch NM, Stewart AF. Regulated and reversible induction of adult human β-cell replication. Diabetes 2012 Feb; 61(2).

Sicari BM, Troxell R, Salim F, Tanwir M, Takane KK, Fiaschi-Taesch N. c-myc and skp2 coordinate p27 degradation, vascular smooth muscle proliferation, and neointima formation induced by the parathyroid hormone-related protein. Endocrinology 2012 Feb; 153(2).

Metukuri MR, Zhang P, Basantani MK, Chin C, Stamateris RE, Alonso LC, Takane KK, Gramignoli R, Strom SC, O'Doherty RM, Stewart AF, Vasavada RC, Garcia-Ocaña A, Scott DK. ChREBP mediates glucose-stimulated pancreatic β-cell proliferation. Diabetes 2012 Aug; 61(8).

Rieck S, Li Z, Sandhu AK, Liu C, Naji AI, Takane KK, Fiaschi-Taesch NM, Stewart AF, Kushner JA, Kaestner KH. Overexpression of hepatocyte nuclear factor 4α initiates cell cycle entry, but it not sufficient to promote ß-cell expansion in human islets.. Molecular Endocrinology 2012; 26: 1590-1602.

Fiaschi-Taesch NM, Kleinberger JW, Salim FG, Troxell R, Wills R, Tanwir M, Casinelli G, Cox AE, Takane KK, Srinivas H, Scott DK, Stewart AF. Cytoplasmic-nuclear trafficking of G1/S cell cycle molecules and adult human β-cell replication: a revised model of human β-cell G1/S control. Diabetes 2013 Jul; 62(7).

Fiaschi-Taesch NM, Kleinberger JW, Salim FG, Troxell R, Wills R, Tanwir M, Casinelli G, Cox AE, Takane KK, Scott DK, Stewart AF. Human pancreatic β-cell G1/S molecule cell cycle atlas. Diabetes 2013 Jul; 62(7).

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Takane did not report having any of the following types of financial relationships with industry during 2013 and/or 2014: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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