A5009062989- Cancer, Hypoxia, and Metabolism
- Protein Tyrosine Phosphatases
- ATP Synthase and ATPases Research
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Adenosine and Purinergic Signaling
- Acute Myeloid Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Protein Degradation and Inhibitors
- Bladder and Urothelial Cancer Treatments
- Endoplasmic Reticulum Stress and Disease
- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Autoimmune Neurological Disorders and Treatments
- Cancer Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Autophagy in Disease and Therapy
- interferon and immune responses
- Blood disorders and treatments
- Cell death mechanisms and regulation
- Neonatal Respiratory Health Research
- Neurofibromatosis and Schwannoma Cases
- Pancreatic function and diabetes
National Institutes of Health
2023-2025
National Cancer Institute
2021-2024
University of Michigan–Ann Arbor
2013-2023
Division of Cancer Epidemiology and Genetics
2021-2022
John Wiley & Sons (United States)
2022
Hudson Institute
2022
Michigan Medicine
2012-2021
Michigan Center for Translational Pathology
2020
Pediatrics and Genetics
2015
Kalpavriksh
2015
The initiation of pancreatic ductal adenocarcinoma (PDA) is linked to activating mutations in KRAS . However, PDA mouse models, expression oncogenic mutant during development gives rise tumors only after a prolonged latency or following induction pancreatitis. Here we describe novel model expressing ataxia telangiectasia group D complementing gene (ATDC, also known as TRIM29 [tripartite motif 29]) that, the presence KRAS, accelerates intraepithelial neoplasia (PanIN) formation and invasive...
Abstract Bladder cancer is a common and deadly malignancy but its treatment has advanced little due to poor understanding of the factors pathways that promote disease. ATDC/TRIM29 highly expressed gene in several lethal tumor types, including bladder tumors, role as pathogenic driver not been established. Here we show overexpression ATDC vivo sufficient drive both noninvasive invasive carcinoma development transgenic mice. ATDC-driven tumors were indistinguishable from human cancers, which...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by therapeutic resistance for which the basis poorly understood. Here, we report that DNA and p53-binding protein ATDC/TRIM29, highly expressed in PDAC, plays a critical role damage signaling radioresistance pancreatic cancer cells. Ataxia-telangiectasia group D-associated gene (ATDC) mediated to ionizing radiation vitro vivo mouse xenograft assays. ATDC was phosphorylated directly MAPKAP kinase 2 (MK2) at Ser550 an ATM-dependent...
Abstract Schwannomatoses (SWN) are distinct cancer predisposition syndromes caused by germline pathogenic variants in the genes NF2, SMARCB1, or LZTR1. There is significant clinical overlap between these with hallmark of increased risk for cranial, spinal and peripheral schwannomas. Neurofibromatosis type 2 was recently renamed as NF2-related SWN most common syndrome bilateral vestibular schwannomas, intradermal meningiomas less commonly ependymoma. SMARCB1-related a familial SWN-syndrome...
Pancreatic ductal adenocarcinoma is a lethal disease characterized by late diagnosis, propensity for early metastasis and resistance to chemotherapy. Little known about the mechanisms that drive innate therapeutic in pancreatic cancer. The ataxia-telangiectasia group D-associated gene (ATDC) overexpressed cancer promotes tumor growth metastasis. Our study reveals increased ATDC levels protect cells from reactive oxygen species (ROS) via stabilization of nuclear factor erythroid 2-related 2...
Abstract Myc proteins regulate cell growth and are oncogenic in many cancers. Although these validated molecular anticancer targets, new therapies aimed at modulating myc have yet to emerge. A benzodiazepine (Bz-423) that was discovered efforts find drugs for lupus found recently antiproliferative effects on Burkitt's lymphoma cells. We now show the basis of Bz-423 is rapid specific depletion c-myc protein, which coupled growth-suppressing key regulators proliferation cycle progression....
Induction of DNA damage by ionizing radiation (IR) and/or cytotoxic chemotherapy is an essential component cancer therapy. The ataxia telangiectasia group D complementing gene (ATDC, also called TRIM29) highly expressed in many malignancies. It participates the response downstream telangiectasia-mutated (ATM) and p38/MK2 promotes cell survival after IR. To elucidate mechanisms ATDC-induced IR protection, we performed a mass spectrometry screen to identify ATDC binding partners. We identified...
Leukemic relapse is believed to be driven by transformed hematopoietic stem cells (HSC) that harbor oncogenic mutations or have lost tumor suppressor function. Recent comprehensive sequencing studies shown predicted activate Ras signaling are highly prevalent in hematologic malignancies and, notably, refractory and relapsed cases. To better understand what drives this clinical phenomenon, we expressed
RAS mutations occur in a broad spectrum of human hematopoietic malignancies. Activating Ras blood cells leads to malignancies mice. In murine stem (HSCs), mutant N-RasG12D activates Stat5 dysregulate cell function. However, the underlying mechanism remains elusive. this study, we demonstrate that activation induced by hyperactive Nras mutant, G12D, is dependent on Jak2 activity. activated HSCs and progenitors (HSPCs), inhibiting with ruxolitinib significantly decreases HSPC...
Cancer remains the number one cause of disease-related mortality in children, and despite advances molecular understanding leukemia targeted therapies, refractory a leading death. It therefore is essential to further define features, e.g., FLT3 alterations KMT2A rearrangements, associated with inferior survival early augment or alter therapeutic strategies improve outcomes.To gain insights into genetic drivers predictive aggressive clinical behavior among pediatric patients, we performed...
Summary Many tissue-specific stem cells require quiescence to sustain cell pool and maintain lifelong tissue integrity. It remains unclear whether protein quality control is required for in when RNA content, synthesis metabolic activities are significantly reduced. Here, we report that endoplasmic reticulum associated degradation (ERAD) preserve the function of quiescent hematopoietic (HSC). The Sel1L/Hrd1 ERAD genes enriched inactive HSCs, conditional knockout Sel1L tissues drives HSCs...
Abstract Purpose Genomic ascertainment of electronic health record-linked exome data in two large biobanks was used to quantify germline pathogenic/likely pathogenic (P/LP) variant prevalence, cancer and survival adults with non- NF1 RAS/mitogen-activated protein kinase genes (RASopathies). Patients Methods Germline RASopathy variants were examined from adult participants UK Biobank (UKBB; n=469,802), Geisinger MyCode (n=167,050) Mount Sinai Bio Me (n=30,470). Variants classified as per...