A5031261791- Melanoma and MAPK Pathways
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- PI3K/AKT/mTOR signaling in cancer
- Molecular Biology Techniques and Applications
- RNA Interference and Gene Delivery
- Cancer Mechanisms and Therapy
- Nonmelanoma Skin Cancer Studies
- Cutaneous Melanoma Detection and Management
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Mitochondrial Function and Pathology
- Single-cell and spatial transcriptomics
- Biomedical Research and Pathophysiology
- Cancer, Lipids, and Metabolism
- Amino Acid Enzymes and Metabolism
- Nanoparticle-Based Drug Delivery
- Skin Protection and Aging
- Synthesis and biological activity
- Gene Regulatory Network Analysis
- Protein Degradation and Inhibitors
- Genomics, phytochemicals, and oxidative stress
- Protein Kinase Regulation and GTPase Signaling
- BRCA gene mutations in cancer
- Advanced Biosensing Techniques and Applications
IIT@MIT
2025
Massachusetts General Hospital
2021-2024
Center for Cancer Research
2023-2024
Harvard University
2021-2023
Moffitt Cancer Center
2023
Whitehead Institute for Biomedical Research
2020-2022
Massachusetts Institute of Technology
2018-2022
The University of Texas MD Anderson Cancer Center
2013-2022
Howard Hughes Medical Institute
2020-2021
Broad Institute
2020-2021
To accelerate the translation of cancer nanomedicine, we used an integrated genomic approach to improve our understanding cellular processes that govern nanoparticle trafficking. We developed a massively parallel screen leverages barcoded, pooled cell lines annotated with multiomic data investigate association patterns across library spanning range formulations clinical potential. identified both materials properties and cell-intrinsic features mediate nanoparticle-cell association. Using...
Significance The mTORC1 eukaryotic cell growth regulator dynamically responds to changes in environmental nutrient levels. While many upstream regulators are known modulate activity, the full complement of these is unknown. Here, using a genome-wide FACS-based CRISPR-Cas9 screen, we identify almost all positive as well others. results our screens highlighted importance mitochondrial health regulation mTORC1, which led us investigate how stress impinges on signaling. Ultimately, found that...
Abstract Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis development through preneoplastic AK stage using matched human samples and solar ultraviolet radiation-driven Hairless mouse model. We...
Vemurafenib and dabrafenib selectively inhibit the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) kinase, resulting in high response rates increased survival melanoma. Approximately 22% of individuals treated with vemurafenib develop cutaneous squamous cell carcinoma (cSCC) during therapy. The prevailing explanation for this is drug-induced paradoxical ERK activation, hyperproliferation. Here we show an unexpected novel effect vemurafenib/PLX4720 suppressing apoptosis through...
The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin activation remain unknown. Here we demonstrated Salt Inducible Kinases (SIKs) orchestrated production downstream PTH signaling. inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation. Whole tissue and single cell transcriptomics both pharmacologic inhibitors regulated a gene module in proximal tubule. increased Cyp27b1 mRNA...
// Charles H. Adelmann 1 , Grace Ching Lili Du Rachael C. Saporito Varun Bansal Lindy J. Pence Roger Liang Woojin Lee Kenneth Y. Tsai 1, 2, 3 Department of Translational Molecular Pathology, The University Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA 2 Dermatology, Graduate School Biomedical Sciences, Correspondence to: Tsai, email: kytsai@mdanderson.org Keywords: BRAF, squamous cell carcinoma, small molecule inhibitor, paradoxical ERK, melanoma Received: November 26, 2015...
Many essential proteins require pyridoxal 5'-phosphate, the active form of vitamin B6, as a cofactor for their activity. These include enzymes important amino acid metabolism, one-carbon polyamine synthesis, erythropoiesis, and neurotransmitter metabolism. A third all mammalian 5'-phosphate-dependent are localized in mitochondria; however, molecular machinery involved regulation mitochondrial 5'-phosphate levels mammals remains unknown. In this study, we used genome-wide CRISPR interference...
Sorafenib is U.S. Food and Drug Adminstration-approved for the treatment of renal cell carcinoma hepatocellular has been combined with numerous other targeted therapies chemotherapies in many cancers. Unfortunately, as RAF inhibitors, patients treated sorafenib have a 5% to 10% rate developing cutaneous squamous (cSCC)/keratoacanthomas. Paradoxical activation extracellular signal-regulated kinase (ERK) BRAF wild-type cells implicated inhibitor-induced cSCC. Here, we report that suppresses...
Protein kinases are mutated or otherwise rendered constitutively active in numerous cancers where they attractive therapeutic targets with well over a dozen kinase inhibitors now being used therapy. While fluorescent sensors have capacity to measure changes activity, surprisingly not been utilized for biomarker studies. A first-generation peptide sensor ERK based on the Sox fluorophore is described. This called ERK-sensor-D1 possesses high activity toward and more than 10-fold discrimination...
SUMMARY Forward genetic screens across hundreds of diverse cancer cell lines have started to define the dependencies proliferating human cells and how these vary by genotype lineage. Most screens, however, been carried out in culture media that poorly resemble metabolite availability blood. To explore medium composition influences gene essentiality, we performed CRISPR-based cultured traditional versus plasma-like (HPLM). Sets medium-dependent fitness genes span several cellular processes...
Abstract In mammalian cells, nutrients and growth factors signal through an array of upstream proteins to regulate the mTORC1 control pathway. Because full complement these has not been systematically identified, we developed a FACS-based CRISPR-Cas9 genetic screening strategy pinpoint genes that activity. Along with almost all known positive components pathway, identified many new impact activity, including DCAF7, CSNK2B, SRSF2, IRS4, CCDC43 , HSD17B10 . Using genome-wide data, generated...
Abstract Multiple cancers regulate oxidative stress by activating the transcription factor NRF2 through mutation of its negative regulator KEAP1. has been studied extensively in KEAP1-mutant cancers, however role this pathway with wildtype KEAP1 remains poorly understood. To answer question, we induced via pharmacological inactivation a panel 50+ non-small lung cancer cell lines. Unexpectedly, marked decreases viability were observed >13% lines—an effect that was completely rescued...
<h3>Background</h3> Overall, 30% of human cancers are driven by mutant RAS proteins, which have historically been difficult to target. While immunotherapy is effective for <i>NRAS</i>-mutant melanoma, resistant disease inadequately addressed, and <i>KRAS</i>-driven carcinomas much less responsive. Oncogenic pathways often key targets inhibition. Even so, resistance the inability safely combine these approaches with immunotherapies remain major challenges. The idea oncogenic pathway agonism...
Abstract To accelerate the translation of cancer nanomedicine, we hypothesize that integrated genomic screens will improve understanding cellular processes governing nanoparticle trafficking. We developed a massively parallel high-throughput screening method leveraging barcoded, pooled cell lines annotated with multi-omic data to investigate association patterns across library spanning range formulations clinical potential. This approach identified both materials properties and...
Abstract While it has been appreciated for decades that lysosomes can import cysteine, its organismal physiology is unclear. Recently, the MFSD12 transmembrane protein was shown to be necessary cysteine into (and melanosomes), enabling study of these processes using genetic tools. Here, we find mice lacking Mfsd12 die between embryonic days 10.5-12.5, suggesting essential organogenesis. Within lysosomes, well known a significant fraction converted cystine (oxidized cysteine), which...
Purpose: The number of immunocompromised patients continues to grow, with improved screening and treatment HIV, as well the increasing use immunosuppressive medications. Such are at increased risks for developing GI opportunistic infections. Even though cytomegalovirus (CMV) remains one most common infection, may have coinfections other rare, fungal infections that be associated high mortality. We present a rare case disseminated Histoplasmosis CMV coinfection in an AIDS patient. A...