Faculty Appointments
Assistant Professor of Medicine
Assistant Professor of Molecular Physiology & Biophysics
Education
Ph.D., Molecular and Systems Pharmacology, Emory University, Atlanta, GeorgiaM.S., Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TennesseeB.S., Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee
Research Description
The Dean lab seeks to understand how nutritional and other environmental factors affect pancreatic islet cell function and proliferation. Islet alpha cells secrete glucagon in response to hypoglycemia leading to increased glucose output by liver, but persons with diabetes often have hyperglucagonemia further contributing to hyperglycemia. Very little is known about signals regulating alpha cells. We have used a mouse model with interrupted glucagon signaling that displays alpha cell hyperplasia and hyperglucagonemia to identify circulating factors that stimulate alpha cell proliferation. We described that the circulating factors are amino acids defining a novel hepatic-pancreatic islet alpha cell axis that is conserved across vertebrate species in our work with both mouse and human pancreatic islets. The Dean lab is current interested in 1) defining the mechanism of how amino acids are sensed by alpha cells to stimulate proliferation and glucagon secretion and 2) investigating the role of amino acids on alpha cell dysfunction in diabetes.
Research Keywords
diabetes; glucagon; liver; pancreatic islet; alpha cell; amino acid; glutamine; arginine; alanine; transport; metabolism; RNASeq; metabolomics; glutaminase; transporters; hyperaminoacidemia; hyperglucagonemia
Publications
Armour SL, Stanley JE, Cantley J, Dean ED, Knudsen JG. Metabolic regulation of glucagon secretion. J Endocrinol [electronic-print]. 2023 Sep 9/1/2023; 259(1): PMID: 37523232, PII: JOE-23-0081, DOI: 10.1530/JOE-23-0081, ISSN: 1479-6805.
Crabtree A, Neikirk K, Marshall AG, Vang L, Whiteside AJ, Williams Q, Altamura CT, Owens TC, Stephens D, Shao B, Koh A, Killion M, Lopez EG, Lam J, Rodriguez B, Mungai M, Stanley J, Dean ED, Koh HJ, Gaddy JA, Scudese E, Sweetwyne MT, Davis J, Zaganjor E, Murray SA, Katti P, Damo SM, Vue Z, Hinton A. Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue. Adv Biol (Weinh) [print-electronic]. 2023 Aug 8/21/2023; e2300186. PMID: 37607124, DOI: 10.1002/adbi.202300186, ISSN: 2701-0198.
Spears E, Stanley JE, Shou M, Yin L, Li X, Dai C, Bradley A, Sellick K, Poffenberger G, Coate KC, Shrestha S, Jenkins R, Sloop KW, Wilson KT, Attie AD, Keller MP, Chen W, Powers AC, Dean ED. Pancreatic islet a cell function and proliferation requires the arginine transporter SLC7A2. BioRxiv. 2023 Aug 8/14/2023; PMID: 37645716, PMCID: PMC10461917, PII: 2023.08.10.552656, DOI: 10.1101/2023.08.10.552656.
Crabtree A, Neikirk K, Marshall AG, Vang L, Whiteside AJ, Williams Q, Altamura CT, Owens TC, Stephens D, Shao B, Koh A, Killion M, Lopez EG, Lam J, Rodriguez B, Mungai M, Stanley J, Dean ED, Koh HJ, Gaddy JA, Scudese E, Sweetwyne M, Davis J, Zaganjor E, Murray SA, Katti P, Damo SM, Vue Z, Hinton A. Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue. BioRxiv. 2023 Aug 8/2/2023; PMID: 37577723, PMCID: PMC10418056, PII: 2023.05.12.540609, DOI: 10.1101/2023.05.12.540609.
Wewer Albrechtsen NJ, Holst JJ, Cherrington AD, Finan B, Gluud LL, Dean ED, Campbell JE, Bloom SR, Tan TM, Knop FK, Müller TD. 100 years of glucagon and 100 more. Diabetologia [print-electronic]. 2023 Aug; 66(8): 1378-94. PMID: 37367959, PII: 10.1007/s00125-023-05947-y, DOI: 10.1007/s00125-023-05947-y, ISSN: 1432-0428.
Wang MY, Dean ED, Quittner-Strom E, Zhu Y, Chowdhury KH, Zhang Z, Zhao S, Li N, Ye R, Lee Y, Zhang Y, Chen S, Yu X, Leonard DC, Poffenberger G, Von Deylen A, McCorkle SK, Schlegel A, Sloop KW, Efanov AM, Gimeno RE, Scherer PE, Powers AC, Unger RH, Holland WL. Glucagon blockade restores functional ß-cell mass in type 1 diabetic mice and enhances function of human islets. Proc Natl Acad Sci U S A. 2021 Mar 3/2/2021; 118(9): PMID: 33619103, PMCID: PMC7936318, PII: 2022142118, DOI: 10.1073/pnas.2022142118, ISSN: 1091-6490.
Dai C, Walker JT, Shostak A, Bouchi Y, Poffenberger G, Hart NJ, Jacobson DA, Calcutt MW, Bottino R, Greiner DL, Shultz LD, McGuinness OP, Dean ED, Powers AC. Dapagliflozin Does Not Directly Affect Human a or ß Cells. Endocrinology. 2020 Aug 8/1/2020; 161(8): PMID: 32428240, PMCID: PMC7375801, PII: 5840747, DOI: 10.1210/endocr/bqaa080, ISSN: 1945-7170.
Dean ED. A Primary Role for a-Cells as Amino Acid Sensors. Diabetes [print-electronic]. 2020 Apr; 69(4): 542-9. PMID: 31653720, PMCID: PMC7085241, PII: dbi19-0021, DOI: 10.2337/dbi19-0021, ISSN: 1939-327X.
Dai C, Walker JT, Shostak A, Padgett A, Spears E, Wisniewski S, Poffenberger G, Aramandla R, Dean ED, Prasad N, Levy SE, Greiner DL, Shultz LD, Bottino R, Powers AC. Tacrolimus- and sirolimus-induced human ß cell dysfunction is reversible and preventable. JCI Insight. 2020 Jan 1/16/2020; 5(1): PMID: 31941840, PMCID: PMC7030815, PII: 130770, DOI: 10.1172/jci.insight.130770, ISSN: 2379-3708.
Dean ED, Vuguin PM, Charron MJ. Glucagon: The Name Says It All, or Not!. Endocrinology. 2019 May 5/1/2019; 160(5): 1359-61. PMID: 31144717, PMCID: PMC6482032, PII: 5434898, DOI: 10.1210/en.2019-00251, ISSN: 1945-7170.
Saunders DC, Brissova M, Phillips N, Shrestha S, Walker JT, Aramandla R, Poffenberger G, Flaherty DK, Weller KP, Pelletier J, Cooper T, Goff MT, Virostko J, Shostak A, Dean ED, Greiner DL, Shultz LD, Prasad N, Levy SE, Carnahan RH, Dai C, Sévigny J, Powers AC. Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic ß Cells for In Vitro and In Vivo Analysis. Cell Metab [print-electronic]. 2019 Mar 3/5/2019; 29(3): 745-754.e4. PMID: 30449685, PMCID: PMC6402969, PII: S1550-4131(18)30639-9, DOI: 10.1016/j.cmet.2018.10.007, ISSN: 1932-7420.
Bozadjieva N, Blandino-Rosano M, Chase J, Dai XQ, Cummings K, Gimeno J, Dean E Danielle, Powers AC, Gittes GK, Rüegg MA, Hall MN, MacDonald PE, Bernal-Mizrachi E. Loss of mTORC1 signaling alters pancreatic a cell mass and impairs glucagon secretion. J. Clin. Invest. 2017 Dec 12/1/2017; 127(12): 4379-93. PMID: 29106387, PMCID: PMC5707167, PII: 90004, DOI: 10.1172/JCI90004, ISSN: 1558-8238.
Dean ED, Li M, Prasad N, Wisniewski SN, Von Deylen A, Spaeth J, Maddison L, Botros A, Sedgeman LR, Bozadjieva N, Ilkayeva O, Coldren A, Poffenberger G, Shostak A, Semich MC, Aamodt KI, Phillips N, Yan H, Bernal-Mizrachi E, Corbin JD, Vickers KC, Levy SE, Dai C, Newgard C, Gu W, Stein R, Chen W, Powers AC. Interrupted Glucagon Signaling Reveals Hepatic a Cell Axis and Role for L-Glutamine in a Cell Proliferation. Cell Metab. 2017 Jun 6/6/2017; 25(6): 1362-1373.e5. PMID: 28591638, PMCID: PMC5572896, PII: S1550-4131(17)30300-5, DOI: 10.1016/j.cmet.2017.05.011, ISSN: 1932-7420.
Dean ED, Unger RH, Holland WL. Glucagon antagonism in islet cell proliferation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2017 Mar 3/21/2017; 114(12): 3006-8. PMID: 28283660, PMCID: PMC5373377, PII: 1700468114, DOI: 10.1073/pnas.1700468114, ISSN: 1091-6490.
Li M, Dean ED, Zhao L, Nicholson WE, Powers AC, Chen W. Glucagon receptor inactivation leads to a-cell hyperplasia in zebrafish. J. Endocrinol. 2015 Nov; 227(2): 93-103. PMID: 26446275, PMCID: PMC4598637, PII: 227/2/93, DOI: 10.1530/JOE-15-0284, ISSN: 1479-6805.
Longuet C, Robledo AM, Dean ED, Dai C, Ali S, McGuinness I, de Chavez V, Vuguin PM, Charron MJ, Powers AC, Drucker DJ. Liver-specific disruption of the murine glucagon receptor produces a-cell hyperplasia: evidence for a circulating a-cell growth factor. Diabetes [print-electronic]. 2013 Apr; 62(4): 1196-205. PMID: 23160527, PMCID: PMC3609565, PII: db11-1605, DOI: 10.2337/db11-1605, ISSN: 1939-327X.
Crabtree A, Neikirk K, Marshall AG, Vang L, Whiteside AJ, Williams Q, Altamura CT, Owens TC, Stephens D, Shao B, Koh A, Killion M, Lopez EG, Lam J, Rodriguez B, Mungai M, Stanley J, Dean ED, Koh HJ, Gaddy JA, Scudese E, Sweetwyne MT, Davis J, Zaganjor E, Murray SA, Katti P, Damo SM, Vue Z, Hinton A. Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue. Adv Biol (Weinh) [print-electronic]. 2023 Aug 8/21/2023; e2300186. PMID: 37607124, DOI: 10.1002/adbi.202300186, ISSN: 2701-0198.
Spears E, Stanley JE, Shou M, Yin L, Li X, Dai C, Bradley A, Sellick K, Poffenberger G, Coate KC, Shrestha S, Jenkins R, Sloop KW, Wilson KT, Attie AD, Keller MP, Chen W, Powers AC, Dean ED. Pancreatic islet a cell function and proliferation requires the arginine transporter SLC7A2. BioRxiv. 2023 Aug 8/14/2023; PMID: 37645716, PMCID: PMC10461917, PII: 2023.08.10.552656, DOI: 10.1101/2023.08.10.552656.
Crabtree A, Neikirk K, Marshall AG, Vang L, Whiteside AJ, Williams Q, Altamura CT, Owens TC, Stephens D, Shao B, Koh A, Killion M, Lopez EG, Lam J, Rodriguez B, Mungai M, Stanley J, Dean ED, Koh HJ, Gaddy JA, Scudese E, Sweetwyne M, Davis J, Zaganjor E, Murray SA, Katti P, Damo SM, Vue Z, Hinton A. Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue. BioRxiv. 2023 Aug 8/2/2023; PMID: 37577723, PMCID: PMC10418056, PII: 2023.05.12.540609, DOI: 10.1101/2023.05.12.540609.
Wewer Albrechtsen NJ, Holst JJ, Cherrington AD, Finan B, Gluud LL, Dean ED, Campbell JE, Bloom SR, Tan TM, Knop FK, Müller TD. 100 years of glucagon and 100 more. Diabetologia [print-electronic]. 2023 Aug; 66(8): 1378-94. PMID: 37367959, PII: 10.1007/s00125-023-05947-y, DOI: 10.1007/s00125-023-05947-y, ISSN: 1432-0428.
Wang MY, Dean ED, Quittner-Strom E, Zhu Y, Chowdhury KH, Zhang Z, Zhao S, Li N, Ye R, Lee Y, Zhang Y, Chen S, Yu X, Leonard DC, Poffenberger G, Von Deylen A, McCorkle SK, Schlegel A, Sloop KW, Efanov AM, Gimeno RE, Scherer PE, Powers AC, Unger RH, Holland WL. Glucagon blockade restores functional ß-cell mass in type 1 diabetic mice and enhances function of human islets. Proc Natl Acad Sci U S A. 2021 Mar 3/2/2021; 118(9): PMID: 33619103, PMCID: PMC7936318, PII: 2022142118, DOI: 10.1073/pnas.2022142118, ISSN: 1091-6490.
Dai C, Walker JT, Shostak A, Bouchi Y, Poffenberger G, Hart NJ, Jacobson DA, Calcutt MW, Bottino R, Greiner DL, Shultz LD, McGuinness OP, Dean ED, Powers AC. Dapagliflozin Does Not Directly Affect Human a or ß Cells. Endocrinology. 2020 Aug 8/1/2020; 161(8): PMID: 32428240, PMCID: PMC7375801, PII: 5840747, DOI: 10.1210/endocr/bqaa080, ISSN: 1945-7170.
Dean ED. A Primary Role for a-Cells as Amino Acid Sensors. Diabetes [print-electronic]. 2020 Apr; 69(4): 542-9. PMID: 31653720, PMCID: PMC7085241, PII: dbi19-0021, DOI: 10.2337/dbi19-0021, ISSN: 1939-327X.
Dai C, Walker JT, Shostak A, Padgett A, Spears E, Wisniewski S, Poffenberger G, Aramandla R, Dean ED, Prasad N, Levy SE, Greiner DL, Shultz LD, Bottino R, Powers AC. Tacrolimus- and sirolimus-induced human ß cell dysfunction is reversible and preventable. JCI Insight. 2020 Jan 1/16/2020; 5(1): PMID: 31941840, PMCID: PMC7030815, PII: 130770, DOI: 10.1172/jci.insight.130770, ISSN: 2379-3708.
Dean ED, Vuguin PM, Charron MJ. Glucagon: The Name Says It All, or Not!. Endocrinology. 2019 May 5/1/2019; 160(5): 1359-61. PMID: 31144717, PMCID: PMC6482032, PII: 5434898, DOI: 10.1210/en.2019-00251, ISSN: 1945-7170.
Saunders DC, Brissova M, Phillips N, Shrestha S, Walker JT, Aramandla R, Poffenberger G, Flaherty DK, Weller KP, Pelletier J, Cooper T, Goff MT, Virostko J, Shostak A, Dean ED, Greiner DL, Shultz LD, Prasad N, Levy SE, Carnahan RH, Dai C, Sévigny J, Powers AC. Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic ß Cells for In Vitro and In Vivo Analysis. Cell Metab [print-electronic]. 2019 Mar 3/5/2019; 29(3): 745-754.e4. PMID: 30449685, PMCID: PMC6402969, PII: S1550-4131(18)30639-9, DOI: 10.1016/j.cmet.2018.10.007, ISSN: 1932-7420.
Bozadjieva N, Blandino-Rosano M, Chase J, Dai XQ, Cummings K, Gimeno J, Dean E Danielle, Powers AC, Gittes GK, Rüegg MA, Hall MN, MacDonald PE, Bernal-Mizrachi E. Loss of mTORC1 signaling alters pancreatic a cell mass and impairs glucagon secretion. J. Clin. Invest. 2017 Dec 12/1/2017; 127(12): 4379-93. PMID: 29106387, PMCID: PMC5707167, PII: 90004, DOI: 10.1172/JCI90004, ISSN: 1558-8238.
Dean ED, Li M, Prasad N, Wisniewski SN, Von Deylen A, Spaeth J, Maddison L, Botros A, Sedgeman LR, Bozadjieva N, Ilkayeva O, Coldren A, Poffenberger G, Shostak A, Semich MC, Aamodt KI, Phillips N, Yan H, Bernal-Mizrachi E, Corbin JD, Vickers KC, Levy SE, Dai C, Newgard C, Gu W, Stein R, Chen W, Powers AC. Interrupted Glucagon Signaling Reveals Hepatic a Cell Axis and Role for L-Glutamine in a Cell Proliferation. Cell Metab. 2017 Jun 6/6/2017; 25(6): 1362-1373.e5. PMID: 28591638, PMCID: PMC5572896, PII: S1550-4131(17)30300-5, DOI: 10.1016/j.cmet.2017.05.011, ISSN: 1932-7420.
Dean ED, Unger RH, Holland WL. Glucagon antagonism in islet cell proliferation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2017 Mar 3/21/2017; 114(12): 3006-8. PMID: 28283660, PMCID: PMC5373377, PII: 1700468114, DOI: 10.1073/pnas.1700468114, ISSN: 1091-6490.
Li M, Dean ED, Zhao L, Nicholson WE, Powers AC, Chen W. Glucagon receptor inactivation leads to a-cell hyperplasia in zebrafish. J. Endocrinol. 2015 Nov; 227(2): 93-103. PMID: 26446275, PMCID: PMC4598637, PII: 227/2/93, DOI: 10.1530/JOE-15-0284, ISSN: 1479-6805.
Longuet C, Robledo AM, Dean ED, Dai C, Ali S, McGuinness I, de Chavez V, Vuguin PM, Charron MJ, Powers AC, Drucker DJ. Liver-specific disruption of the murine glucagon receptor produces a-cell hyperplasia: evidence for a circulating a-cell growth factor. Diabetes [print-electronic]. 2013 Apr; 62(4): 1196-205. PMID: 23160527, PMCID: PMC3609565, PII: db11-1605, DOI: 10.2337/db11-1605, ISSN: 1939-327X.