Elizabeth P. Henske, MD

Elizabeth P. Henske, MD

Medical Oncology

Contact Information

Office Phone Number

617-632-6328

Fax

617-632-2165

Appointments

(877) 332-4294 (new)

Biography

Elizabeth P. Henske, MD

Researcher

Physician

Director, Center for LAM Research and Clinical Care
Professor of Medicine, Harvard Medical School

Centers/Programs

Clinical Interests

Genitourinary tumors, Lymphangioleiomyomatosis (LAM), Tuberous sclerosis complex

Board Certification

  • Internal Medicine, 1998
  • Medical Oncology

Fellowship

  • Brigham and Women's Hospital, Cancer Genetics Research
  • Massachusetts General Hospital, Hematology/Oncology

Residency

  • Massachusetts General Hospital, Internal Medicine

Medical School

  • Harvard Medical School

Research

    Cancer genetics, renal carcinoma, tuberous sclerosis complex, LAM

    The Henske laboratory is focused on the cell biology and biochemistry of Tuberous Sclerosis Complex (TSC), Lymphangioleiomyomatosis (LAM) and Birt-Hogg-Dube Syndrome (BHD).Tuberous Sclerosis Complex (TSC) is a tumor suppressor gene syndrome with a wide spectrum of devastating clinical manifestations, many of which are age-related. TSC is often diagnosed in childhood when patients present with infantile seizures, mental retardation, or autism. Cardiac rhabdomyomas, often observed in infancy, spontaneously regress. In the kidney, benign angiomyolipomas and cysts occur frequently, and malignant angiomyolipomas and renal cell carcinomas are less common. A particularly striking manifestation of TSC is pulmonary lymphangioleiomyomatosis (LAM), which is observed almost exclusively in women. LAM can also occur in women who do not have TSC (sporadic LAM). LAM is characterized by benign smooth muscle cell proliferation in the lungs, which thicken the alveolar wall and reduce gas exchange, and by cystic degeneration of the lungs, resulting in lung collapse. LAM patients often become oxygen-dependent.The TSC Signaling Pathway. TSC2 encodes tuberin, TSC1 encodes hamartin. Rheb (Ras homology enriched in brain) is the target of TSC2's highly conserved GTPase-activating domain. By inhibiting Rheb, the TSC1/TSC2 complex also inhibits the mammalian target of rapamycin (mTOR). mTOR is a kinase that regulates protein synthesis, in part via its regulation of a second kinase, p70S6 kinase (S6K). The phosphorylation of p70S6K by mTOR stimulates translational initiation and contributes to cell growth.Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant tumor suppressor gene syndrome characterized by hamartomas of skin follicles (fibrofolliculomas), spontaneous pneumothorax (lung collapse), and renal cell carcinoma (RCC). Unlike most other genetic disorders associated with renal tumors, BHD patients develop multiple histologic tumor types, including oncocytomas (which are considered benign) and chromophobe, clear cell and papillary carcinomas. The BHD gene was cloned in 2002. Nearly all reported human germline BHD mutations are predicted to result in premature protein truncation.

    Publications

      • TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex. Nat Commun. 2024 Jan 09; 15(1):406. View in: Pubmed

      • Kidney cancer: Links between hereditary syndromes and sporadic tumorigenesis. Semin Diagn Pathol. 2024 Jan; 41(1):1-7. View in: Pubmed

      • Bi-steric mTORC1 inhibitors induce apoptotic cell death in tumor models with hyperactivated mTORC1. J Clin Invest. 2023 11 01; 133(21). View in: Pubmed

      • Chromophobe renal cell carcinoma Cancer Cell. 2023 08 14; 41(8):1383-1388. View in: Pubmed

      • Lymphangioleiomyomatosis: circulating levels of FGF23 and pulmonary diffusion. J Bras Pneumol. 2023; 49(2):e20220356. View in: Pubmed

      • mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion. Nat Commun. 2023 03 03; 14(1):1214. View in: Pubmed

      • Spectrum of germline and somatic mitochondrial DNA variants in Tuberous Sclerosis Complex. Front Genet. 2022; 13:917993. View in: Pubmed

      • Epigenomic charting and functional annotation of risk loci in renal cell carcinoma. Nat Commun. 2023 01 21; 14(1):346. View in: Pubmed

      • Drug Inhibition of Redox Factor-1 Restores Hypoxia-Driven Changes in Tuberous Sclerosis Complex 2 Deficient Cells. Cancers (Basel). 2022 Dec 15; 14(24). View in: Pubmed

      • Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex. iScience. 2022 Nov 18; 25(11):105458. View in: Pubmed

      • Angiotensin II receptor type 1 blockade regulates Klotho expression to induce TSC2-deficient cell death. J Biol Chem. 2022 11; 298(11):102580. View in: Pubmed

      • Lymphangioleiomyomatosis (LAM) Cell Atlas. Thorax. 2023 01; 78(1):85-87. View in: Pubmed

      • Keeping up with the Rag GTPases. Nat Cell Biol. 2022 09; 24(9):1330-1331. View in: Pubmed

      • Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment. Nat Commun. 2022 08 26; 13(1):5018. View in: Pubmed

      • Hypersensitivity to ferroptosis in chromophobe RCC is mediated by a glutathione metabolic dependency and cystine import via solute carrier family 7 member 11. Proc Natl Acad Sci U S A. 2022 07 12; 119(28):e2122840119. View in: Pubmed

      • Protease activity sensors enable real-time treatment response monitoring in lymphangioleiomyomatosis. Eur Respir J. 2022 04; 59(4). View in: Pubmed

      • Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2022 02 22; 119(8). View in: Pubmed

      • ETV2 regulates PARP-1 binding protein to induce ER stress-mediated death in tuberin-deficient cells. Life Sci Alliance. 2022 05; 5(5). View in: Pubmed

      • Modeling tuberous sclerosis with organoids. Science. 2022 01 28; 375(6579):382-383. View in: Pubmed

      • Seventh BHD international symposium: recent scientific and clinical advancement. Oncotarget. 2022; 13:173-181. View in: Pubmed

      • A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo. Nat Commun. 2021 11 11; 12(1):6496. View in: Pubmed

      • The TSC Complex-mTORC1 Axis: From Lysosomes to Stress Granules and Back. Front Cell Dev Biol. 2021; 9:751892. View in: Pubmed

      • Renal Cell Carcinoma in Tuberous Sclerosis Complex. Genes (Basel). 2021 10 08; 12(10). View in: Pubmed

      • Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells. Proc Natl Acad Sci U S A. 2021 09 28; 118(39). View in: Pubmed

      • Genetic risk assessment for hereditary renal cell carcinoma: Clinical consensus statement. Cancer. 2021 Nov 01; 127(21):3957-3966. View in: Pubmed

      • mTORC1 is a mechanosensor that regulates surfactant function and lung compliance during ventilator-induced lung injury. JCI Insight. 2021 07 22; 6(14). View in: Pubmed

      • TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism. Nat Commun. 2021 07 12; 12(1):4245. View in: Pubmed

      • TSC2 Interacts with HDLBP/Vigilin and Regulates Stress Granule Formation. Mol Cancer Res. 2021 08; 19(8):1389-1397. View in: Pubmed

      • The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell. 2021 04 15; 184(8):2256. View in: Pubmed

      • Therapeutic Targeting of DGKA-Mediated Macropinocytosis Leads to Phospholipid Reprogramming in Tuberous Sclerosis Complex. Cancer Res. 2021 04 15; 81(8):2086-2100. View in: Pubmed

      • mTORC1 hyperactivation in lymphangioleiomyomatosis leads to ACE2 upregulation in type II pneumocytes: implications for COVID-19. Eur Respir J. 2021 02; 57(2). View in: Pubmed

      • Kidney intercalated cells and the transcription factor FOXi1 drive cystogenesis in tuberous sclerosis complex. Proc Natl Acad Sci U S A. 2021 02 09; 118(6). View in: Pubmed

      • Correction: p62/SQSTM1 Cooperates with Hyperactive mTORC1 to Regulate Glutathione Production, Maintain Mitochondrial Integrity, and Promote Tumorigenesis. Cancer Res. 2020 Dec 01; 80(23):5424. View in: Pubmed

      • MITF is a driver oncogene and potential therapeutic target in kidney angiomyolipoma tumors through transcriptional regulation of CYR61. Oncogene. 2021 01; 40(1):112-126. View in: Pubmed

      • Tumour predisposition and cancer syndromes as models to study gene-environment interactions. Nat Rev Cancer. 2020 09; 20(9):533-549. View in: Pubmed

      • Celecoxib in lymphangioleiomyomatosis: results of a phase I clinical trial. Eur Respir J. 2020 05; 55(5). View in: Pubmed

      • Chromophobe renal cell carcinoma: New genetic and metabolic insights. Urol Oncol. 2020 08; 38(8):678-681. View in: Pubmed

      • New Developments in the Pathogenesis of Pulmonary Cysts in Birt-Hogg-Dubé Syndrome. Semin Respir Crit Care Med. 2020 04; 41(2):247-255. View in: Pubmed

      • IMPDH inhibitors for antitumor therapy in tuberous sclerosis complex. JCI Insight. 2020 04 09; 5(7). View in: Pubmed

      • Mesenchymal folliculin is required for alveolar development: implications for cystic lung disease in Birt-Hogg-Dubé syndrome. Thorax. 2020 06; 75(6):486-493. View in: Pubmed

      • Generalised mosaicism for TSC2 mutation in isolated lymphangioleiomyomatosis. Eur Respir J. 2019 10; 54(4). View in: Pubmed

      • Loss of FLCN inhibits canonical WNT signaling via TFE3. Hum Mol Genet. 2019 10 01; 28(19):3270-3281. View in: Pubmed

      • Tumors with TSC mutations are sensitive to CDK7 inhibition through NRF2 and glutathione depletion. J Exp Med. 2019 11 04; 216(11):2635-2652. View in: Pubmed

      • Immunotherapy for Lymphangioleiomyomatosis and Tuberous Sclerosis: Progress and Future Directions. Chest. 2019 12; 156(6):1062-1067. View in: Pubmed

      • Rapamycin-upregulated miR-29b promotes mTORC1-hyperactive cell growth in TSC2-deficient cells by downregulating tumor suppressor retinoic acid receptor ß (RARß). Oncogene. 2019 12; 38(49):7367-7383. View in: Pubmed

      • Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells. Chest. 2019 12; 156(6):1137-1148. View in: Pubmed

      • A genome-wide association study implicates NR2F2 in lymphangioleiomyomatosis pathogenesis. Eur Respir J. 2019 06; 53(6). View in: Pubmed

      • Allosteric and ATP-Competitive Inhibitors of mTOR Effectively Suppress Tumor Progression-Associated Epithelial-Mesenchymal Transition in the Kidneys of Tsc2+/- Mice. Neoplasia. 2019 08; 21(8):731-739. View in: Pubmed

      • The Genetics of Pneumothorax. Am J Respir Crit Care Med. 2019 06 01; 199(11):1344-1357. View in: Pubmed

      • The Codon 72 TP53 Polymorphism Contributes to TSC Tumorigenesis through the Notch-Nodal Axis. Mol Cancer Res. 2019 08; 17(8):1639-1651. View in: Pubmed

      • Serum endostatin levels are associated with diffusion capacity and with tuberous sclerosis- associated lymphangioleiomyomatosis. Orphanet J Rare Dis. 2019 03 29; 14(1):72. View in: Pubmed

      • Vitamin D binding protein: a new biomarker of disease severity in lymphangioleiomyomatosis. Eur Respir J. 2018 11; 52(5). View in: Pubmed

      • Renal disease in tuberous sclerosis complex: pathogenesis and therapy. Nat Rev Nephrol. 2018 11; 14(11):704-716. View in: Pubmed

      • Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease. Am J Respir Crit Care Med. 2018 10 01; 198(7):850-858. View in: Pubmed

      • Vps34-mediated macropinocytosis in Tuberous Sclerosis Complex 2-deficient cells supports tumorigenesis. Sci Rep. 2018 09 21; 8(1):14161. View in: Pubmed

      • Circulating Biomarkers From the Phase 1 Trial of Sirolimus and Autophagy Inhibition for Patients With Lymphangioleiomyomatosis. Chest. 2018 11; 154(5):1070-1082. View in: Pubmed

      • Pulmonary manifestations in tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018 09; 178(3):326-337. View in: Pubmed

      • The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. Cell Rep. 2018 Jun 19; 23(12):3698. View in: Pubmed

      • Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma. Proc Natl Acad Sci U S A. 2018 07 03; 115(27):E6274-E6282. View in: Pubmed

      • TSC2 regulates microRNA biogenesis via mTORC1 and GSK3ß. Hum Mol Genet. 2018 05 01; 27(9):1654-1663. View in: Pubmed

      • Characterization of lymphangioleiomyomatosis patients with discordance between spirometric and diffusion measurements of pulmonary function. Sarcoidosis Vasc Diffuse Lung Dis. 2018; 35(3):206-212. View in: Pubmed

      • TSC2-deficient tumors have evidence of T cell exhaustion and respond to anti-PD-1/anti-CTLA-4 immunotherapy. JCI Insight. 2018 04 19; 3(8). View in: Pubmed

      • The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. Cell Rep. 2018 04 03; 23(1):313-326.e5. View in: Pubmed

      • The Verge of Collapse. N Engl J Med. 2018 Mar 29; 378(13):e18. View in: Pubmed

      • Familial pneumothorax: towards precision medicine. Thorax. 2018 03; 73(3):270-276. View in: Pubmed

      • Emerging biomarkers of lymphangioleiomyomatosis. Expert Rev Respir Med. 2018 02; 12(2):95-102. View in: Pubmed

      • Notch transactivates Rheb to maintain the multipotency of TSC-null cells. Nat Commun. 2017 11 29; 8(1):1848. View in: Pubmed

      • mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability. Cancer Cell. 2017 11 13; 32(5):624-638.e5. View in: Pubmed

      • Human Pluripotent Stem Cell-Derived TSC2-Haploinsufficient Smooth Muscle Cells Recapitulate Features of Lymphangioleiomyomatosis. Cancer Res. 2017 10 15; 77(20):5491-5502. View in: Pubmed

      • Rapamycin-induced miR-21 promotes mitochondrial homeostasis and adaptation in mTORC1 activated cells. Oncotarget. 2017 Sep 12; 8(39):64714-64727. View in: Pubmed

      • Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is mediated via NPC1 and LDL-R. Oncotarget. 2017 Jun 13; 8(24):38099-38112. View in: Pubmed

      • A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations. Cancer Cell. 2017 06 12; 31(6):820-832.e3. View in: Pubmed

      • p62/SQSTM1 Cooperates with Hyperactive mTORC1 to Regulate Glutathione Production, Maintain Mitochondrial Integrity, and Promote Tumorigenesis. Cancer Res. 2017 06 15; 77(12):3255-3267. View in: Pubmed

      • Spontaneous Pneumothoraces in Patients with Birt-Hogg-Dubé Syndrome. Ann Am Thorac Soc. 2017 May; 14(5):706-713. View in: Pubmed

      • Haploinsufficiency in tumor predisposition syndromes: altered genomic transcription in morphologically normal cells heterozygous for VHL or TSC mutation. Oncotarget. 2017 Mar 14; 8(11):17628-17642. View in: Pubmed

      • Aberrant SYK Kinase Signaling Is Essential for Tumorigenesis Induced by TSC2 Inactivation. Cancer Res. 2017 03 15; 77(6):1492-1502. View in: Pubmed

      • Sirolimus and Autophagy Inhibition in Lymphangioleiomyomatosis: Results of a Phase I Clinical Trial. Chest. 2017 06; 151(6):1302-1310. View in: Pubmed

      • The effect of mTOR inhibitors on respiratory infections in lymphangioleiomyomatosis. Eur Respir Rev. 2017 Jan; 26(143). View in: Pubmed

      • New developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex. J Pathol. 2017 Jan; 241(2):219-225. View in: Pubmed

      • Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis. JCI Insight. 2016 Nov 17; 1(19):e86629. View in: Pubmed

      • Inactivation of Tsc2 in Mesoderm-Derived Cells Causes Polycystic Kidney Lesions and Impairs Lung Alveolarization. Am J Pathol. 2016 12; 186(12):3261-3272. View in: Pubmed

      • Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. Am J Respir Crit Care Med. 2016 09 15; 194(6):748-61. View in: Pubmed

      • Whole Exome Sequencing Identifies TSC1/TSC2 Biallelic Loss as the Primary and Sufficient Driver Event for Renal Angiomyolipoma Development. PLoS Genet. 2016 08; 12(8):e1006242. View in: Pubmed

      • Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2(-) Tumor Related to Lymphangioleiomyomatosis. Am J Pathol. 2016 07; 186(7):1825-1836. View in: Pubmed

      • Tuberous sclerosis complex. Nat Rev Dis Primers. 2016 05 26; 2:16035. View in: Pubmed

      • Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference. Pediatr Neurol. 2016 07; 60:1-12. View in: Pubmed

      • Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma. Cell Rep. 2016 Mar 15; 14(10):2476-89. View in: Pubmed

      • Mechanisms of pulmonary cyst pathogenesis in Birt-Hogg-Dube syndrome: The stretch hypothesis. Semin Cell Dev Biol. 2016 Apr; 52:47-52. View in: Pubmed

      • Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016; 12(1):1-222. View in: Pubmed

      • Exosomes mediate the acquisition of the disease phenotypes by cells with normal genome in tuberous sclerosis complex. Oncogene. 2016 06 09; 35(23):3027-36. View in: Pubmed

      • Unjamming and cell shape in the asthmatic airway epithelium. Nat Mater. 2015 Oct; 14(10):1040-8. View in: Pubmed

      • Tuberous sclerosis complex 2 loss increases lysophosphatidylcholine synthesis in lymphangioleiomyomatosis. Am J Respir Cell Mol Biol. 2015 Jul; 53(1):33-41. View in: Pubmed

      • Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study. Eur Respir J. 2015 Sep; 46(3):783-94. View in: Pubmed

      • The next breakthrough in LAM clinical trials may be their design: challenges in design and execution of future LAM clinical trials. Expert Rev Respir Med. 2015 Apr; 9(2):195-204. View in: Pubmed

      • Targeted deletion of Tsc1 causes fatal cardiomyocyte hyperplasia independently of afterload. Cardiovasc Pathol. 2015 Mar-Apr; 24(2):80-93. View in: Pubmed

      • Therapeutic targeting of cellular metabolism in cells with hyperactive mTORC1: a paradigm shift. Mol Cancer Res. 2015 Jan; 13(1):3-8. View in: Pubmed

      • Regulation of YAP by mTOR and autophagy reveals a therapeutic target of tuberous sclerosis complex. J Exp Med. 2014 Oct 20; 211(11):2249-63. View in: Pubmed

      • High-throughput drug screen identifies chelerythrine as a selective inducer of death in a TSC2-null setting. Mol Cancer Res. 2015 Jan; 13(1):50-62. View in: Pubmed

      • The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014 Sep 08; 26(3):319-330. View in: Pubmed

      • Folliculin regulates cell-cell adhesion, AMPK, and mTORC1 in a cell-type-specific manner in lung-derived cells. Physiol Rep. 2014 Aug 01; 2(8). View in: Pubmed

      • Role of BRAFV600E in the first preclinical model of multifocal infiltrating myopericytoma development and microenvironment. J Natl Cancer Inst. 2014 Aug; 106(8). View in: Pubmed

      • Renal cell carcinoma in tuberous sclerosis complex. Am J Surg Pathol. 2014 Jul; 38(7):895-909. View in: Pubmed

      • Filling the holes in cystic kidney disease research. Clin J Am Soc Nephrol. 2014 Oct 07; 9(10):1799-801. View in: Pubmed

      • Estradiol promotes pentose phosphate pathway addiction and cell survival via reactivation of Akt in mTORC1 hyperactive cells. Cell Death Dis. 2014 May 15; 5:e1231. View in: Pubmed

      • Towards personalised therapy for lymphangioleiomyomatosis: lessons from cancer. Eur Respir Rev. 2014 Mar 01; 23(131):30-5. View in: Pubmed

      • Kinase mTOR: regulation and role in maintenance of cellular homeostasis, tumor development, and aging. Biochemistry (Mosc). 2014 Feb; 79(2):88-101. View in: Pubmed

      • Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells. J Exp Med. 2014 Jan 13; 211(1):15-28. View in: Pubmed

      • Autophagy-dependent metabolic reprogramming sensitizes TSC2-deficient cells to the antimetabolite 6-aminonicotinamide. Mol Cancer Res. 2014 Jan; 12(1):48-57. View in: Pubmed

      • Tuberous sclerosis complex, mTOR, and the kidney: report of an NIDDK-sponsored workshop. Am J Physiol Renal Physiol. 2014 Feb 01; 306(3):F279-83. View in: Pubmed

      • Integration of mTOR and estrogen-ERK2 signaling in lymphangioleiomyomatosis pathogenesis. Proc Natl Acad Sci U S A. 2013 Sep 10; 110(37):14960-5. View in: Pubmed

      • TORC1 signaling is governed by two negative regulators in fission yeast. Genetics. 2013 Oct; 195(2):457-68. View in: Pubmed

      • Reply: Characterization of lymphangioleiomyomatosis as a neoplastic disease. Am J Respir Crit Care Med. 2013 Aug 01; 188(3):398-9. View in: Pubmed

      • Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis. Am J Respir Cell Mol Biol. 2013 Jul; 49(1):135-42. View in: Pubmed

      • The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell. 2013 May 09; 153(4):840-54. View in: Pubmed

      • Autophagy: mechanisms, regulation, and its role in tumorigenesis. Biochemistry (Mosc). 2013 Apr; 78(4):355-67. View in: Pubmed

      • Metabolic reprogramming in polycystic kidney disease. Nat Med. 2013 Apr; 19(4):407-9. View in: Pubmed

      • MicroRNA-21 is induced by rapamycin in a model of tuberous sclerosis (TSC) and lymphangioleiomyomatosis (LAM). PLoS One. 2013; 8(3):e60014. View in: Pubmed

      • Lymphangioleiomyomatosis: calling it what it is: a low-grade, destructive, metastasizing neoplasm. Am J Respir Crit Care Med. 2012 Dec 15; 186(12):1210-2. View in: Pubmed

      • Folliculin, the product of the Birt-Hogg-Dube tumor suppressor gene, interacts with the adherens junction protein p0071 to regulate cell-cell adhesion. PLoS One. 2012; 7(11):e47842. View in: Pubmed

      • Lymphangioleiomyomatosis - a wolf in sheep's clothing. J Clin Invest. 2012 Nov; 122(11):3807-16. View in: Pubmed

      • Real-time monitoring of tumorigenesis, dissemination, & drug response in a preclinical model of lymphangioleiomyomatosis/tuberous sclerosis complex. PLoS One. 2012; 7(6):e38589. View in: Pubmed

      • Getting to the finish line with mTORC1-targeted therapy. J Clin Invest. 2012 Jun; 122(6):1970-2. View in: Pubmed

      • Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012 Apr; 8(4):445-544. View in: Pubmed

      • TORC1 activation and autophagy inhibition: opposing forces in Rheb-driven tumorigenesis. Cell Cycle. 2011 Nov 15; 10(22):3803-4. View in: Pubmed

      • Autophagy: an 'Achilles' heel of tumorigenesis in TSC and LAM. Autophagy. 2011 Nov; 7(11):1400-1. View in: Pubmed

      • Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent. Proc Natl Acad Sci U S A. 2011 Jul 26; 108(30):12455-60. View in: Pubmed

      • Rabin8 Protein Interacts with GTPase Rheb and Inhibits Phosphorylation of Ser235/Ser236 in Small Ribosomal Subunit Protein S6. Acta Naturae. 2011 Jul; 3(3):71-6. View in: Pubmed

      • Tuberous sclerosis complex and lymphangioleiomyomatosis: miles to go, promises to keep. Ann Intern Med. 2011 Jun 21; 154(12):840-1. View in: Pubmed

      • Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis. EMBO Mol Med. 2011 Apr; 3(4):189-200. View in: Pubmed

      • Loss of the Birt-Hogg-Dubé tumor suppressor results in apoptotic resistance due to aberrant TGFß-mediated transcription. Oncogene. 2011 Jun 02; 30(22):2534-46. View in: Pubmed

      • mTOR activation, lymphangiogenesis, and estrogen-mediated cell survival: the "perfect storm" of pro-metastatic factors in LAM pathogenesis. Lymphat Res Biol. 2010 Mar; 8(1):43-9. View in: Pubmed

      • The International LAM Registry: a component of an innovative web-based clinician, researcher, and patient-driven rare disease research platform. Lymphat Res Biol. 2010 Mar; 8(1):81-7. View in: Pubmed

      • Mammalian target of rapamycin signaling and autophagy: roles in lymphangioleiomyomatosis therapy. Proc Am Thorac Soc. 2010 Feb; 7(1):48-53. View in: Pubmed

      • The evolutionarily conserved TSC/Rheb pathway activates Notch in tuberous sclerosis complex and Drosophila external sensory organ development. J Clin Invest. 2010 Jan; 120(1):93-102. View in: Pubmed

      • The p53 target Plk2 interacts with TSC proteins impacting mTOR signaling, tumor growth and chemosensitivity under hypoxic conditions. Cell Cycle. 2009 Dec 15; 8(24):4168-75. View in: Pubmed

      • Differential requirement of CAAX-mediated posttranslational processing for Rheb localization and signaling. Oncogene. 2010 Jan 21; 29(3):380-91. View in: Pubmed

      • The role of the Birt-Hogg-Dubé protein in mTOR activation and renal tumorigenesis. Oncogene. 2009 Apr 02; 28(13):1594-604. View in: Pubmed

      • Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells. Proc Natl Acad Sci U S A. 2009 Feb 24; 106(8):2635-40. View in: Pubmed

      • The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway. Hum Mol Genet. 2009 Jan 01; 18(1):151-63. View in: Pubmed

      • Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53. EMBO J. 2007 Nov 28; 26(23):4812-23. View in: Pubmed

      • mTOR is activated in the majority of malignant melanomas. J Invest Dermatol. 2008 Apr; 128(4):980-7. View in: Pubmed

      • HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell. 2007 Jun 29; 129(7):1351-63. View in: Pubmed

      • The Birt-Hogg-Dube and tuberous sclerosis complex homologs have opposing roles in amino acid homeostasis in Schizosaccharomyces pombe. J Biol Chem. 2007 Aug 24; 282(34):24583-90. View in: Pubmed

      • Analysis of published PKD1 gene sequence variants. Nat Genet. 2007 Apr; 39(4):427-8. View in: Pubmed

      • Activation of the mTOR signaling pathway in renal clear cell carcinoma. J Urol. 2007 Jan; 177(1):346-52. View in: Pubmed

      • Estrogen-induced activation of mammalian target of rapamycin is mediated via tuberin and the small GTPase Ras homologue enriched in brain. Cancer Res. 2006 Oct 01; 66(19):9461-6. View in: Pubmed

      • The tuberous sclerosis complex. N Engl J Med. 2006 Sep 28; 355(13):1345-56. View in: Pubmed

      • Rheb inhibits C-raf activity and B-raf/C-raf heterodimerization. J Biol Chem. 2006 Sep 01; 281(35):25447-56. View in: Pubmed

      • Frequent [corrected] hyperphosphorylation of ribosomal protein S6 [corrected] in lymphangioleiomyomatosis-associated angiomyolipomas. Mod Pathol. 2006 Jun; 19(6):839-46. View in: Pubmed

      • Mutation detection in tumor suppressor genes using archival tissue specimens. Methods Mol Med. 2006; 126:185-96. View in: Pubmed

      • Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner. Hum Mol Genet. 2006 Jan 15; 15(2):287-97. View in: Pubmed

      • Tuberous sclerosis complex: linking growth and energy signaling pathways with human disease. Oncogene. 2005 Nov 14; 24(50):7475-81. View in: Pubmed

      • The role of tuberin in cellular differentiation: are B-Raf and MAPK involved? Ann N Y Acad Sci. 2005 Nov; 1059:168-73. View in: Pubmed

      • Pas1, a G1 cyclin, regulates amino acid uptake and rescues a delay in G1 arrest in Tsc1 and Tsc2 mutants in Schizosaccharomyces pombe. Hum Mol Genet. 2005 Oct 01; 14(19):2851-8. View in: Pubmed

      • Tuberous sclerosis and the kidney: from mesenchyme to epithelium, and beyond. Pediatr Nephrol. 2005 Jul; 20(7):854-7. View in: Pubmed

      • Altered gene expression in phenotypically normal renal cells from carriers of tumor suppressor gene mutations. Cancer Biol Ther. 2004 Dec; 3(12):1313-21. View in: Pubmed

      • Use of RNA amplification in the optimal characterization of global gene expression using cDNA microarrays. J Cell Physiol. 2004 Dec; 201(3):359-65. View in: Pubmed

      • The genetic basis of kidney cancer: why is tuberous sclerosis complex often overlooked? Curr Mol Med. 2004 Dec; 4(8):825-31. View in: Pubmed

      • Aberrant cellular differentiation and migration in renal and pulmonary tuberous sclerosis complex. J Child Neurol. 2004 Sep; 19(9):710-5. View in: Pubmed

      • Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent. J Biol Chem. 2004 Jul 16; 279(29):29930-7. View in: Pubmed

      • Tsc1+ and tsc2+ regulate arginine uptake and metabolism in Schizosaccharomyces pombe. J Biol Chem. 2004 Mar 26; 279(13):12706-13. View in: Pubmed

      • Metastasis of benign tumor cells in tuberous sclerosis complex. Genes Chromosomes Cancer. 2003 Dec; 38(4):376-81. View in: Pubmed

      • Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B. J Biol Chem. 2003 Dec 19; 278(51):51372-9. View in: Pubmed

      • Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways. Am J Physiol Lung Cell Mol Physiol. 2004 Apr; 286(4):L694-700. View in: Pubmed

      • Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma. Lancet. 2003 Apr 19; 361(9366):1348-9. View in: Pubmed

      • Renal angiomyolipomas from patients with sporadic lymphangiomyomatosis contain both neoplastic and non-neoplastic vascular structures. Am J Pathol. 2003 Feb; 162(2):491-500. View in: Pubmed

      • Tuberin, the tuberous sclerosis complex 2 tumor suppressor gene product, regulates Rho activation, cell adhesion and migration. Oncogene. 2002 Dec 05; 21(55):8470-6. View in: Pubmed

      • Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism. Am J Respir Crit Care Med. 2003 Apr 01; 167(7):976-82. View in: Pubmed

      • Expression of wild type and mutant TSC2, but not TSC1, causes an increase in the G1 fraction of the cell cycle in HEK293 cells. J Med Genet. 2002 Sep; 39(9):676-80. View in: Pubmed

      • Tuberous sclerosis-associated lesions of the kidney, brain, and skin are angiogenic neoplasms. J Am Acad Dermatol. 2002 Mar; 46(3):376-80. View in: Pubmed

      • Mutational analysis of the von hippel lindau gene in clear cell renal carcinomas from tuberous sclerosis complex patients. Mod Pathol. 2002 Mar; 15(3):205-10. View in: Pubmed

      • Chromosome 16 loss of heterozygosity in tuberous sclerosis and sporadic lymphangiomyomatosis. Am J Respir Crit Care Med. 2001 Oct 15; 164(8 Pt 1):1537-40. View in: Pubmed

      • A novel missense mutation in the GTPase activating protein homology region of TSC2 in two large families with tuberous sclerosis complex. J Med Genet. 2001 May; 38(5):347-9. View in: Pubmed

      • Selective alterations in glutamate and GABA receptor subunit mRNA expression in dysplastic neurons and giant cells of cortical tubers. Ann Neurol. 2001 Jan; 49(1):67-78. View in: Pubmed

      • The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis. Am J Respir Crit Care Med. 2001 Jan; 163(1):253-8. View in: Pubmed

      • Pulmonary lymphangioleiomyomatosis in a man. Am J Respir Crit Care Med. 2000 Aug; 162(2 Pt 1):749-52. View in: Pubmed

      • Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2000 May 23; 97(11):6085-90. View in: Pubmed

      • Frequent estrogen and progesterone receptor immunoreactivity in renal angiomyolipomas from women with pulmonary lymphangioleiomyomatosis. Chest. 2000 Jan; 117(1):25-30. View in: Pubmed

      • Mutational analysis of the tuberous sclerosis gene TSC2 in patients with pulmonary lymphangioleiomyomatosis. J Med Genet. 2000 Jan; 37(1):55-7. View in: Pubmed

      • New developments in the neurobiology of the tuberous sclerosis complex. Neurology. 1999 Oct 22; 53(7):1384-90. View in: Pubmed

      • The expression of hamartin, the product of the TSC1 gene, in normal human tissues and in TSC1- and TSC2-linked angiomyolipomas. Mod Pathol. 1999 May; 12(5):539-45. View in: Pubmed

      • Renal cell carcinoma in children with diffuse cystic hyperplasia of the kidneys. Pediatr Dev Pathol. 1999 May-Jun; 2(3):270-4. View in: Pubmed

      • Renal angiomyolipomas, cysts, and cancer in tuberous sclerosis complex. Semin Pediatr Neurol. 1998 Dec; 5(4):269-75. View in: Pubmed

      • Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex. Cancer. 1998 Nov 15; 83(10):2208-16. View in: Pubmed

      • Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles. Cancer Res. 1998 Nov 01; 58(21):4766-70. View in: Pubmed

      • Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance. Ann Hum Genet. 1998 Jul; 62(Pt 4):277-85. View in: Pubmed

      • Frequent progesterone receptor immunoreactivity in tuberous sclerosis-associated renal angiomyolipomas. Mod Pathol. 1998 Jul; 11(7):665-8. View in: Pubmed

      • Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis. Am J Hum Genet. 1998 Apr; 62(4):810-5. View in: Pubmed

      • Apparent renal cell carcinomas in tuberous sclerosis are heterogeneous: the identification of malignant epithelioid angiomyolipoma. Am J Surg Pathol. 1998 Feb; 22(2):180-7. View in: Pubmed

      • Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. Am J Pathol. 1997 Dec; 151(6):1639-47. View in: Pubmed

      • Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997 Aug 08; 277(5327):805-8. View in: Pubmed

      • Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1. Ann Hum Genet. 1997 Jul; 61(Pt 4):299-305. View in: Pubmed

      • Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis. J Clin Invest. 1997 Jan 15; 99(2):194-9. View in: Pubmed

      • Aggressive variants of chromophobe renal cell carcinoma. Cancer. 1996 Oct 15; 78(8):1756-61. View in: Pubmed

      • Tuberous sclerosis-associated renal cell carcinoma. Clinical, pathological, and genetic features. Am J Pathol. 1996 Oct; 149(4):1201-8. View in: Pubmed

      • Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. Am J Hum Genet. 1996 Aug; 59(2):400-6. View in: Pubmed

      • Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas. Genes Chromosomes Cancer. 1995 Aug; 13(4):295-8. View in: Pubmed

      • A 5.4-Mb continuous pulsed-field gel electrophoresis map of human 9q34.1 between ABL and D9S114, including the tuberous sclerosis (TSC1) region. Genomics. 1995 Jul 01; 28(1):105-8. View in: Pubmed

      • Cosmid contigs spanning 9q34 including the candidate region for TSC1. Eur J Hum Genet. 1995; 3(2):65-77. View in: Pubmed

      • Identification of VAV2 on 9q34 and its exclusion as the tuberous sclerosis gene TSC1. Ann Hum Genet. 1995 01; 59(1):25-37. View in: Pubmed

      • The human actin-regulatory protein cap G: gene structure and chromosome location. Genomics. 1994 Oct; 23(3):560-5. View in: Pubmed

      • Analysis of interphase cells for the Philadelphia translocation using painting probe made by inter-Alu-polymerase chain reaction from a radiation hybrid. Blood. 1994 Apr 15; 83(8):2268-73. View in: Pubmed

      • A high-resolution linkage map of human 9q34.1. Genomics. 1993 Sep; 17(3):587-91. View in: Pubmed

      • Actin-binding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28. Genomics. 1993 Aug; 17(2):496-8. View in: Pubmed

      • Detection of variant Ph-positive chronic myelogenous leukemia involving chromosomes 1, 9, and 22 by fluorescence in situ hybridization. Cancer Genet Cytogenet. 1993 Feb; 65(2):100-3. View in: Pubmed

      • A radiation-reduced hybrid cell line containing 5 Mb/17 cM of human DNA from 9q34. Genomics. 1992 Jul; 13(3):841-4. View in: Pubmed

      • Construction of a GT polymorphism map of human 9q. Genomics. 1992 Feb; 12(2):229-40. View in: Pubmed

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      75 Francis Street Boston, MA 02115
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      Brigham and Women's Hospital

      Location Avtar

      Brigham and Women's Hospital

      75 Francis Street One Blackfan Circle, Karp Building, 6th Floor Boston, MA 02215
      Get Direction
      42.3362, -71.1067

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