Overview
Endocytic Membrane Trafficking
Insulin regulates the storage of dietary glucose by stimulating its uptake into muscle and fat. Insulin increases glucose uptake into these cells by recruiting vesicles containing the GLUT4 glucose transporter to the cell surface. Thus, insulin controls glucose uptake by regulating GLUT4 trafficking between the interior and cell surface. Understanding how insulin regulates GLUT4 traffic is key for understanding the molecular changes underlying type 2 diabetes. We use quantitative optical microscopy to study insulin-regulated membrane trafficking. The main objectives of our work are to characterize the GLUT4 trafficking pathway in the presence and absence of insulin, and to identify how the insulin-signal transduction regulates the movement of GLUT4 vesicles. In addition to studies of GLUT4 trafficking, I am also interested in more basic questions of membrane trafficking, specifically a more detailed understanding of the molecular mechanisms of clathrin-mediated internalization from the cell surface and the mechanisms for return of endocytosed proteins back to the plasma membrane. Further information: http://www.med.cornell.edu/biochem/mcgraw
Highlights
- 1Cell reports · 2022
- 2Nature communications · 2023
- 3Molecular biology of the cell · 2020
Publications
Funding
Active
5 grants- MPIR01DK142926-01A1GIP receptor signaling mechanismsNational Institute of Diabetes and Digestive and Kidney Diseases · 2026–2031
- PIR01DK144473-01A1A basic mechanism contributing to human insulin resistance and diabetes: role of the essential amino acid sensor SLC36A4 in GLUT4 trafficking in adipocytesNational Institute of Diabetes and Digestive and Kidney Diseases · 2026–2028
- KPT32DK131957-01A1Research Training in Endocrinology and MetabolismNational Institute of Diabetes and Digestive and Kidney Diseases · 2023–2028Training
- Co-IR01CA271545-01A1Immunoregulatory role of lung-resident club cell factors in lung cancerNational Cancer Institute · 2023–2028
Completed grants (20)
- PIR01DK125699-04Insulin control of GLUT4 traffic to the plasma membrane of adipocytesNational Institute of Diabetes and Digestive and Kidney Diseases · 2020–2025
- MPIUG3CA244697-01Intercepting progression from pre-invasive to invasive lung adenocarcinomaNational Cancer Institute · 2019–2025· 2 renewals
- Co-INYGC 211479-01Ethnic based differences between Asian and Caucasian patients in genomic, transcriptomic and immune profiles of pre-invasive and invasive adenocarcinoma of the lungNew York Genome Center Inc. · 2020–2024
- Co-IW81XWH2110309The Mechanistic Basis Of Radiation Induced Immunomodulation In Early Non-Small Cell Lung CancerU.S. Department of Defense · 2021–2024No publications yet
- KPS10OD032317-01Hypoxic incubator for physiological cell culture researchOffice of the Director, NIH · 2022–2023
- PIW81XWH-19-1-0422Targeting ART1, a novel immune checkpoint, for the treatment of lung cancerU.S. Department of Defense · 2019–2023
- PIR01DK118342-04GIP receptor: The role of post-activation receptor behavior for the incretin effectNational Institute of Diabetes and Digestive and Kidney Diseases · 2018–2023
- Co-IJ&J Biopharma 213315-02Molecular and cellular profiling of preinvasive and minimally invasive lesions to understand the biology underlying progression from indolent to more invasive tumorsJohnson & Johnson · 2020–2022
- PIPI 200899-01Pfizer Research Service AgreementPfizer Inc. · 2019–2022BioPharma Alliance
- PIPI 190410-01Mechanisms regulating GLUT4 translocation in skeletal musclePfizer Inc. · 2018–2020Contract
- KPFTB 16010147-03ART1: A Novel Therapeutic Target For the Prevention of Metastases From Non-Small Cell Lung CancerFree to Breathe · 2015–2019
- PIR56DK096925-05A1Functional Studies of the Incretin GIP Receptor in AdipocytesNational Institute of Diabetes and Digestive and Kidney Diseases · 2017–2018
- PIR01DK052852-19Insulin Regulated Membrane TraffickingNational Institute of Diabetes and Digestive and Kidney Diseases · 2011–2018· 2 renewals
- PIR01DK096925-03Functional Studies of the Incretin GIP Receptor in AdipocytesNational Institute of Diabetes and Digestive and Kidney Diseases · 2012–2017
- Sub-PIR01DK098002-03Metabolic Effects of Adipose LipogenesisNational Institute of Diabetes and Digestive and Kidney Diseases · 2013–2017 · via Beth Israel Deaconess Medical Center, Inc.
- PIT32HD041895-05Pediatric Endocrinology Research Training ProgramNICHD · 2002–2008 · via NIH RePORTER
Clinical research
Completed & closed trials (1)
- PITargeting ART1, a novel immune checkpoint, for the treatment of lung cancerWeill Medical College of Cornell University · IRB STUDY CLOSURE (as of 2024)
Available technologies
News mentions
- Gene Signature May Predict Response to Immunotherapy for Non-Small Cell Lung CancerFebruary 23, 2024
A new study identified a set of 140 genes that may help predict enhanced disease-free survival in patients with non-small cell lung cancer (NSCLC) treated with a combination of immunotherapy and low-dose radiation.
- Genetic Signature May Predict Response to Immunotherapy for Non-Small Cell Lung CancerFebruary 23, 2024
A new study identified a...
- Immunotherapy and Radiation Combo Shows Improved Outcomes for Non-small Cell Lung CancerJanuary 11, 2024
A new study reported that patients with non-small cell lung cancer (NSCLC) treated with a combination of low-dose radiation and immunotherapy had higher progression-free survival compared to patients who received immunotherapy alone two years after treatment.
- Specific Genetic Variant May Help Prevent ObesityDecember 7, 2023
A preclinical study by Weill Cornell Medicine investigators shows that a specific human genetic variant of a receptor that stimulates insulin release may help individuals be more resistant to obesity. The researchers discovered that this variant behaves differently in the cell which may contribute to more efficient metabolism.
- NIH Grant Funds Cancer Prevention Vaccine ResearchNovember 11, 2022
A multidisciplinary team of Weill Cornell Medicine researchers has received a five-year $5.7 million grant from the National Cancer Institute at the National Institutes of Health to fund a center aimed at developing messenger RNA (mRNA) vaccines to deter cancer development in at-risk groups.
Show 2 more mentions
- A Potential New Target for Cancer ImmunotherapiesMarch 16, 2022
Tumors can use an enzyme called ART1 to thwart antitumor immune cells, making the enzyme a promising new target for immunity-boosting cancer treatments, according to a study from researchers at Weill Cornell Medicine and Albert Einstein College of Medicine. In the study, published Mar. 16 in Science Translational Medicine, the researchers found strong evidence that ART1, when expressed on tumor cells, can modify a receptor on tumor-fighting immune cells in a way that triggers the death of these immune cells. In animal models of cancer, blocking ART1 increased the presence of the tumor-fighting immune cells within tumors and slowed or stopped tumor growth. “These findings should allow us to add to our medicinal toolkit for enhancing the antitumor immune response, to benefit cancer patients,” said study co-corresponding author Dr. Timothy McGraw, professor of biochemistry and of biochemistry in cardiothoracic surgery and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “Our main focus in this study was lung cancer, but there is evidence that this immune-evasion mechanism is at work also in other kinds of cancer,” said co-corresponding author Dr. Sandra Demaria, professor of radiation oncology and of pathology and laboratory medicine and a member of the Meyer Cancer Center at Weill Cornell Medicine. “This is an excellent example of how translational science should work. We first found ART1 expressed in the tumors of patients with lung cancer. In the lab, we discovered that ART1 helps to block the anti-tumor immune response, specifically by inducing death of anti-tumor T cells. We then developed a therapeutic antibody that blocks the function of ART1, allows the immune system to fight the cancer and ultimately prolongs survival in tumor models,” said senior author Dr. Brendon Stiles, formerly of Weill Cornell Medicine and now chief of the Division of Thoracic Surgery and Surgical Oncology and associate director of surgical services at…
- Cancer Moonshot Grant Funds Research into Discovering Targets for Lung Cancer Prevention StrategiesNovember 21, 2019
A prestigious Cancer Moonshot grant from the National Cancer Institute’s Immuno-Oncology Translational Network will enable investigators to explore the mechanisms that allow slow-growing lung cancer lesions to progress into aggressive malignancies and identify new therapeutic strategies to intercept the transition.
Mentoring
PhD · 1
- ALAnudari LetianBiochemistry & Structural Biology (PhD) · Class of 2022
Postdoc · 8
- IPIsabella ParidaPostdoc mentee · 2022–2024
- HKHarsh KumarPostdoc mentee · 2021–2023
- ARAnuttoma RayPostdoc mentee · 2021–2022
- MBMaria Belen Picatoste BotijaPostdoc mentee · 2015–2020
- NCNatasha ChaudharyPostdoc mentee · 2014–2018
- NANazish AbdullahPostdoc mentee · 2014–2018