Lee S. Weinstein, M.D.

• Chief: Metabolic Diseases Branch
• Section Chief: Signal Transduction Section, Metabolic Diseases Branch

Scientific Focus Areas: Clinical Research, Genetics and Genomics, Molecular Biology and Biochemistry, Molecular Pharmacology, Neuroscience

leew@mail.nih.gov 301-402-2923 Add to Contacts

Publications

A selection of recent and significant publications can be viewed below.

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G(q)α/G(11)α deficiency in dorsomedial hypothalamus leads to obesity resulting from decreased energy expenditure and impaired sympathetic nerve activity.

Wilson EA, Sun H, Cui Z, Jahnke MT, Pandey M, Metzger P, Gavrilova O, Chen M, Weinstein LS.

Am J Physiol Endocrinol Metab (2021 Feb 1) 320:E270-E280. Abstract/Full Text

Gsα deficiency in the dorsomedial hypothalamus underlies obesity associated with Gsα mutations.

Chen M, Shrestha YB, Podyma B, Cui Z, Naglieri B, Sun H, Ho T, Wilson EA, Li YQ, Gavrilova O, Weinstein LS.

J Clin Invest (2017 Feb 1) 127:500-510. Abstract/Full Text

G(q/11)α and G(s)α mediate distinct physiological responses to central melanocortins.

Li YQ, Shrestha Y, Pandey M, Chen M, Kablan A, Gavrilova O, Offermanns S, Weinstein LS.

J Clin Invest (2016 Jan) 126:40-9. Abstract/Full Text

Gsα deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight.

Li YQ, Shrestha YB, Chen M, Chanturiya T, Gavrilova O, Weinstein LS.

Proc Natl Acad Sci U S A (2016 Jan 12) 113:446-51. Abstract/Full Text

Parathyroid Hormone Resistance and Autoantibodies to the PTH1 Receptor.

Mandl A, Burbelo PD, Di Pasquale G, Tay YS, Welch J, Lionakis MS, Rosenzweig SD, Waldman MA, Warner BM, Walitt B, Collins MT, Balow JE, Chiorini JA, Simonds WF, Agarwal SK, Blau JE, Weinstein LS.

N Engl J Med (2021 Nov 18) 385:1974-1980. Abstract/Full Text

Additional Publications

Frequency and consequence of the recurrent YY1 p.T372R mutation in sporadic insulinomas.

Parekh VI, Modali SD, Welch J, Simonds WF, Weinstein LS, Kebebew E, Agarwal SK.

Endocr Relat Cancer (2018 May) 25:L31-L35. Abstract/Full Text

Reoperative Surgery in Patients with Multiple Endocrine Neoplasia Type 1 Associated Primary Hyperparathyroidism.

Keutgen XM, Nilubol N, Agarwal S, Welch J, Cochran C, Marx SJ, Weinstein LS, Simonds WF, Kebebew E.

Ann Surg Oncol (2016 Dec) 23:701-707. Abstract/Full Text

A patient with MEN1 typical features and MEN2-like features.

El-Maouche D, Welch J, Agarwal SK, Weinstein LS, Simonds WF, Marx SJ.

Int J Endocr Oncol (2016 May) 3:89-95. Abstract/Full Text

Limited Parathyroidectomy in Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism: A Setup for Failure.

Nilubol N, Weinstein LS, Simonds WF, Jensen RT, Marx SJ, Kebebew E.

Ann Surg Oncol (2016 Feb) 23:416-23. Abstract/Full Text

Ablation of the Stimulatory G Protein α-Subunit in Renal Proximal Tubules Leads to Parathyroid Hormone-Resistance With Increased Renal Cyp24a1 mRNA Abundance and Reduced Serum 1,25-Dihydroxyvitamin D.

Zhu Y, He Q, Aydin C, Rubera I, Tauc M, Chen M, Weinstein LS, Marshansky V, Jüppner H, Bastepe M.

Endocrinology (2016 Feb) 157:497-507. Abstract/Full Text

Gsα Deficiency in the Ventromedial Hypothalamus Enhances Leptin Sensitivity and Improves Glucose Homeostasis in Mice on a High-Fat Diet.

Berger A, Kablan A, Yao C, Ho T, Podyma B, Weinstein LS, Chen M.

Endocrinology (2016 Feb) 157:600-10. Abstract/Full Text

Gαs regulates asymmetric cell division of cortical progenitors by controlling Numb mediated Notch signaling suppression.

Liu K, Lin Q, Wei Y, He R, Shao X, Ding Z, Zhang J, Zhu M, Weinstein LS, Hong Y, Li H, Li H.

Neurosci Lett (2015 Jun 15) 597:97-103. Abstract/Full Text

Inactivation of a Gα(s)-PKA tumour suppressor pathway in skin stem cells initiates basal-cell carcinogenesis.

Iglesias-Bartolome R, Torres D, Marone R, Feng X, Martin D, Simaan M, Chen M, Weinstein LS, Taylor SS, Molinolo AA, Gutkind JS.

Nat Cell Biol (2015 Jun) 17:793-803. Abstract/Full Text

Loss of Gsα early in the osteoblast lineage favors adipogenic differentiation of mesenchymal progenitors and committed osteoblast precursors.

Sinha P, Aarnisalo P, Chubb R, Ono N, Fulzele K, Selig M, Saeed H, Chen M, Weinstein LS, Pajevic PD, Kronenberg HM, Wu JY.

J Bone Miner Res (2014 Nov) 29:2414-26. Abstract/Full Text

Role of G(s)α in central regulation of energy and glucose metabolism.

Weinstein LS.

Horm Metab Res (2014 Nov) 46:841-4. Abstract/Full Text

G-protein stimulatory subunit alpha and Gq/11α G-proteins are both required to maintain quiescent stem-like chondrocytes.

Chagin AS, Vuppalapati KK, Kobayashi T, Guo J, Hirai T, Chen M, Offermanns S, Weinstein LS, Kronenberg HM.

Nat Commun (2014 Apr 30) 5:3673. Abstract/Full Text

Cyclin B1/Cdk1 coordinates mitochondrial respiration for cell-cycle G2/M progression.

Wang Z, Fan M, Candas D, Zhang TQ, Qin L, Eldridge A, Wachsmann-Hogiu S, Ahmed KM, Chromy BA, Nantajit D, Duru N, He F, Chen M, Finkel T, Weinstein LS, Li JJ.

Dev Cell (2014 Apr 28) 29:217-32. Abstract/Full Text

Postnatal establishment of allelic Gαs silencing as a plausible explanation for delayed onset of parathyroid hormone resistance owing to heterozygous Gαs disruption.

Turan S, Fernandez-Rebollo E, Aydin C, Zoto T, Reyes M, Bounoutas G, Chen M, Weinstein LS, Erben RG, Marshansky V, Bastepe M.

J Bone Miner Res (2014 Mar) 29:749-60. Abstract/Full Text

Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a.

Muniyappa R, Warren MA, Zhao X, Aney SC, Courville AB, Chen KY, Brychta RJ, Germain-Lee EL, Weinstein LS, Skarulis MC.

J Clin Endocrinol Metab (2013 Nov) 98:E1796-801. Abstract/Full Text

Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification.

Regard JB, Malhotra D, Gvozdenovic-Jeremic J, Josey M, Chen M, Weinstein LS, Lu J, Shore EM, Kaplan FS, Yang Y.

Nat Med (2013 Nov) 19:1505-12. Abstract/Full Text

Agonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons.

Nakashima A, Takeuchi H, Imai T, Saito H, Kiyonari H, Abe T, Chen M, Weinstein LS, Yu CR, Storm DR, Nishizumi H, Sakano H.

Cell (2013 Sep 12) 154:1314-25. Abstract/Full Text

Myelopoiesis is regulated by osteocytes through Gsα-dependent signaling.

Fulzele K, Krause DS, Panaroni C, Saini V, Barry KJ, Liu X, Lotinun S, Baron R, Bonewald L, Feng JQ, Chen M, Weinstein LS, Wu JY, Kronenberg HM, Scadden DT, Divieti Pajevic P.

Blood (2013 Feb 7) 121:930-9. Abstract/Full Text

Gsα deficiency in the paraventricular nucleus of the hypothalamus partially contributes to obesity associated with Gsα mutations.

Chen M, Berger A, Kablan A, Zhang J, Gavrilova O, Weinstein LS.

Endocrinology (2012 Sep) 153:4256-65. Abstract/Full Text

Development and treatment of tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1B.

Neary NM, El-Maouche D, Hopkins R, Libutti SK, Moses AM, Weinstein LS.

J Clin Endocrinol Metab (2012 Sep) 97:3025-30. Abstract/Full Text

Preoperative localizing studies for initial parathyroidectomy in MEN1 syndrome: is there any benefit?

Nilubol N, Weinstein L, Simonds WF, Jensen RT, Phan GQ, Hughes MS, Libutti SK, Marx S, Kebebew E.

World J Surg (2012 Jun) 36:1368-74. Abstract/Full Text

Sleeping parathyroid tumor: rapid hyperfunction after removal of the dominant tumor.

Yavuz S, Simonds WF, Weinstein LS, Collins MT, Kebebew E, Nilubol N, Phan GQ, Libutti SK, Remaley AT, Van Deventer M, Marx SJ.

J Clin Endocrinol Metab (2012 Jun) 97:1834-41. Abstract/Full Text

Wnt/β-catenin signaling is differentially regulated by Gα proteins and contributes to fibrous dysplasia.

Regard JB, Cherman N, Palmer D, Kuznetsov SA, Celi FS, Guettier JM, Chen M, Bhattacharyya N, Wess J, Coughlin SR, Weinstein LS, Collins MT, Robey PG, Yang Y.

Proc Natl Acad Sci U S A (2011 Dec 13) 108:20101-6. Abstract/Full Text

Improved fatigue resistance in Gsα-deficient and aging mouse skeletal muscles due to adaptive increases in slow fibers.

Feng HZ, Chen M, Weinstein LS, Jin JP.

J Appl Physiol (1985) (2011 Sep) 111:834-43. Abstract/Full Text

Absence of the glucagon-like peptide-1 receptor does not affect the metabolic phenotype of mice with liver-specific G(s)α deficiency.

Chen M, Mema E, Kelleher J, Nemechek N, Berger A, Wang J, Xie T, Gavrilova O, Drucker DJ, Weinstein LS.

Endocrinology (2011 Sep) 152:3343-50. Abstract/Full Text

Gsα enhances commitment of mesenchymal progenitors to the osteoblast lineage but restrains osteoblast differentiation in mice.

Wu JY, Aarnisalo P, Bastepe M, Sinha P, Fulzele K, Selig MK, Chen M, Poulton IJ, Purton LE, Sims NA, Weinstein LS, Kronenberg HM.

J Clin Invest (2011 Sep) 121:3492-504. Abstract/Full Text

Effects of deficiency of the G protein Gsα on energy and glucose homeostasis.

Chen M, Nemechek NM, Mema E, Wang J, Weinstein LS.

Eur J Pharmacol (2011 Jun 11) 660:119-24. Abstract/Full Text

Transgenic overexpression of the extra-large Gsα variant XLαs enhances Gsα-mediated responses in the mouse renal proximal tubule in vivo.

Liu Z, Segawa H, Aydin C, Reyes M, Erben RG, Weinstein LS, Chen M, Marshansky V, Fröhlich LF, Bastepe M.

Endocrinology (2011 Apr) 152:1222-33. Abstract/Full Text

Pancreas-specific Gsalpha deficiency has divergent effects on pancreatic alpha- and beta-cell proliferation.

Xie T, Chen M, Weinstein LS.

J Endocrinol (2010 Sep) 206:261-9. Abstract/Full Text

G(s)alpha deficiency in adipose tissue leads to a lean phenotype with divergent effects on cold tolerance and diet-induced thermogenesis.

Chen M, Chen H, Nguyen A, Gupta D, Wang J, Lai EW, Pacak K, Gavrilova O, Quon MJ, Weinstein LS.

Cell Metab (2010 Apr 7) 11:320-30. Abstract/Full Text

The role of GNAS and other imprinted genes in the development of obesity.

Weinstein LS, Xie T, Qasem A, Wang J, Chen M.

Int J Obes (Lond) (2010 Jan) 34:6-17. Abstract/Full Text

Reoperation for parathyroid adenoma: a contemporary experience.

Powell AC, Alexander HR, Chang R, Marx SJ, Skarulis M, Pingpank JF, Bartlett DL, Hughes M, Weinstein LS, Simonds WF, Collins MF, Shawker T, Chen CC, Reynolds J, Cochran C, Steinberg SM, Libutti SK.

Surgery (2009 Dec) 146:1144-55. Abstract/Full Text

Haematopoietic stem cells depend on Galpha(s)-mediated signalling to engraft bone marrow.

Adams GB, Alley IR, Chung UI, Chabner KT, Jeanson NT, Lo Celso C, Marsters ES, Chen M, Weinstein LS, Lin CP, Kronenberg HM, Scadden DT.

Nature (2009 May 7) 459:103-7. Abstract/Full Text

G(s)alpha deficiency in skeletal muscle leads to reduced muscle mass, fiber-type switching, and glucose intolerance without insulin resistance or deficiency.

Chen M, Feng HZ, Gupta D, Kelleher J, Dickerson KE, Wang J, Hunt D, Jou W, Gavrilova O, Jin JP, Weinstein LS.

Am J Physiol Cell Physiol (2009 Apr) 296:C930-40. Abstract/Full Text

Removal of the N-terminal extension of cardiac troponin I as a functional compensation for impaired myocardial beta-adrenergic signaling.

Feng HZ, Chen M, Weinstein LS, Jin JP.

J Biol Chem (2008 Nov 28) 283:33384-93. Abstract/Full Text

Osteoblastic regulation of B lymphopoiesis is mediated by Gs{alpha}-dependent signaling pathways.

Wu JY, Purton LE, Rodda SJ, Chen M, Weinstein LS, McMahon AP, Scadden DT, Kronenberg HM.

Proc Natl Acad Sci U S A (2008 Nov 4) 105:16976-81. Abstract/Full Text

A gastrointestinal stromal tumor in a patient with multiple endocrine neoplasia type 2A and metastatic medullary thyroid cancer to the ovaries.

Malek R, McCarthy-Keith D, Levens ED, Merino MJ, DeCherney AH, Weinstein LS.

Endocr Pract (2008 Oct) 14:898-901. Abstract/Full Text

Severe obesity and insulin resistance due to deletion of the maternal Gsalpha allele is reversed by paternal deletion of the Gsalpha imprint control region.

Xie T, Chen M, Gavrilova O, Lai EW, Liu J, Weinstein LS.

Endocrinology (2008 May) 149:2443-50. Abstract/Full Text

Beta cell-specific deficiency of the stimulatory G protein alpha-subunit Gsalpha leads to reduced beta cell mass and insulin-deficient diabetes.

Xie T, Chen M, Zhang QH, Ma Z, Weinstein LS.

Proc Natl Acad Sci U S A (2007 Dec 4) 104:19601-6. Abstract/Full Text

Studies of the regulation and function of the Gs alpha gene Gnas using gene targeting technology.

Weinstein LS, Xie T, Zhang QH, Chen M.

Pharmacol Ther (2007 Aug) 115:271-91. Abstract/Full Text

The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations.

Ozawa A, Agarwal SK, Mateo CM, Burns AL, Rice TS, Kennedy PA, Quigley CM, Simonds WF, Weinstein LS, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ.

J Clin Endocrinol Metab (2007 May) 92:1948-51. Abstract/Full Text

Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudohypoparathyroidism may implicate paternal imprinting of Galpha(s) in the development of human obesity.

Long DN, McGuire S, Levine MA, Weinstein LS, Germain-Lee EL.

J Clin Endocrinol Metab (2007 Mar) 92:1073-9. Abstract/Full Text

Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the gsalpha gene.

Yu S, Yu D, Lee E, Eckhaus M, Lee R, Corria Z, Accili D, Westphal H, Weinstein LS.

Proc Natl Acad Sci U S A (1998 Jul 21) 95:8715-20. Abstract/Full Text

Activating mutations of the stimulatory G protein in the McCune-Albright syndrome.

Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM.

N Engl J Med (1991 Dec 12) 325:1688-95. Abstract/Full Text

Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis.

Weinstein LS, Gejman PV, Friedman E, Kadowaki T, Collins RM, Gershon ES, Spiegel AM.

Proc Natl Acad Sci U S A (1990 Nov) 87:8287-90. Abstract/Full Text

Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1.

Friedman E, Sakaguchi K, Bale AE, Falchetti A, Streeten E, Zimering MB, Weinstein LS, McBride WO, Nakamura Y, Brandi ML.

N Engl J Med (1989 Jul 27) 321:213-8. Abstract/Full Text