A5013938996- Renal cell carcinoma treatment
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Renal and related cancers
- CNS Lymphoma Diagnosis and Treatment
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cancer Genomics and Diagnostics
- Parkinson's Disease Mechanisms and Treatments
- Bladder and Urothelial Cancer Treatments
- Genetic Neurodegenerative Diseases
- Paraquat toxicity studies and treatments
- Pancreatic and Hepatic Oncology Research
- Mitochondrial Function and Pathology
- Immune cells in cancer
- Peroxisome Proliferator-Activated Receptors
- Neuroinflammation and Neurodegeneration Mechanisms
- Inflammatory mediators and NSAID effects
- Single-cell and spatial transcriptomics
- Ion Channels and Receptors
- Sexual Differentiation and Disorders
- Medical History and Research
- Retinoids in leukemia and cellular processes
- Ovarian cancer diagnosis and treatment
- Medicinal plant effects and applications
- Tuberous Sclerosis Complex Research
University of Rochester Medical Center
2006-2025
Memorial Sloan Kettering Cancer Center
2021-2023
University of Rochester
2006-2023
Mitochondrial dysfunction has been reported in both familial and sporadic Parkinson's disease (PD). However, effective therapy targeting this pathway is currently inadequate. Recent studies suggest that manipulating the processes of mitochondrial fission fusion considerable potential for treating human diseases. To determine therapeutic impact these pathways on PD, we used two complementary mouse models impairments as seen PD. We show here blocking neuroprotective PTEN-induced putative...
Aquaporin-4 (AQP4) is a primary influx route for water during brain edema formation. Here, we provide evidence that swelling triggers Ca 2+ signaling in astrocytes and deletion of the Aqp4 gene markedly interferes with these events. Using vivo two-photon imaging, show hypoosmotic stress (20% reduction osmolarity) initiates astrocytic spikes reduces signals. The signals are partly dependent on activation P2 purinergic receptors, which was judged from effects appropriate antagonists applied to...
Toxic organic cations can damage nigrostriatal dopaminergic pathways as seen in most parkinsonian syndromes and some cases of illicit drug exposure. Here, we show that the cation transporter 3 (Oct3) is expressed nondopaminergic cells adjacent to both soma terminals midbrain neurons. We hypothesized Oct3 contributes by bidirectionally regulating local bioavailability toxic species. Consistent with this view, deletion pharmacological inhibition hampers release 1-methyl-4-phenylpyridinium from...
The herbicide paraquat (PQ) has increasingly been reported in epidemiological studies to enhance the risk of developing Parkinson's disease (PD). Furthermore, case-control report that individuals with genetic variants dopamine transporter ( DAT , SLC6A ) have a higher PD when exposed PQ. However, it remains topic debate whether PQ can enter (DA) neurons through DAT. We here mechanism by which is transported DAT: In its native divalent cation state, 2+ not substrate for DAT; however,...
Abnormalities in mitochondrial function and epigenetic regulation are thought to be instrumental Huntington's disease (HD), a fatal genetic disorder caused by an expanded polyglutamine track the protein huntingtin. Given lack of effective therapies for HD, we sought assess neuroprotective properties energizing ketone body, D-β-hydroxybutyrate (DβHB), 3-nitropropionic acid (3-NP) toxic R6/2 model HD. In mice treated with 3-NP, complex II inhibitor, infusion DβHB attenuates motor deficits,...
Abstract Background Intratumoral heterogeneity (ITH) is a hallmark of clear cell renal carcinoma (ccRCC) that reflects the trajectory evolution and influences clinical prognosis. Here, we seek to elucidate how ITH tumor during immune checkpoint inhibitor (ICI) treatment can lead therapy resistance. Methods completed single-arm pilot study examine safety feasibility neoadjuvant nivolumab in patients with localized RCC. Primary endpoints were nivolumab. Then, spatiotemporally profiled genomic...
Abstract It is poorly understood how the tumor immune microenvironment influences disease recurrence in localized clear-cell renal cell carcinoma (ccRCC). Here we performed whole-transcriptomic profiling of 236 tumors from patients assigned to placebo-only arm a randomized, adjuvant clinical trial for high-risk ccRCC. Unbiased pathway analysis identified myeloid-derived IL6 as key mediator. Furthermore, novel myeloid gene signature strongly correlated with and overall survival on uni-...
596 Background: The American Cancer Society estimates 14,390 deaths from kidney cancer in 2024 Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of cancer, and 5-10% patients with chRCC develop metastatic disease. Being able to prognosticate which tumors are aggressive vs. indolent a significant unmet need. Methods: All partial radical nephrectomies performed at our institution between 2012-2018 were queried. Cases stage pT1a-pT3a N0M0 time surgery minimum three-year...
Introduction In clear cell renal carcinoma (ccRCC), tumor-associated macrophage (TAM) induction of CD8+T cells into a terminally exhausted state has been implicated as major mechanism immunotherapy resistance, but deeper biological understanding is necessary. Methods Primary ccRCC tumor samples were obtained from 97 patients between 2004 and 2018. Multiplex immunofluorescence using lymphoid myeloid markers was performed in seven regions interest per patient across three predefined zones,...
Succinate dehydrogenase-deficient and fumarate hydratase-deficient renal cell carcinomas (SDHRCC FHRCC) are rare kidney cancers driven by loss of TCA cycle enzymes.To define compare the genomic metabolomic hallmarks SDHRCC FHRCC.We analyzed FHRCC tumors with either immunohistochemical evidence protein expression or genomically confirmed biallelic inactivation SDHA/B/C/D/AF2 FH.Somatic alterations were identified using clinical pipelines, allele-specific copy number (CNAs) FACETS. Mass...
Abstract Purpose: We report our experience with next-generation sequencing to characterize the landscape of actionable genomic alterations in renal cell carcinoma (RCC). Experimental Design: A query institutional clinical database (MSK-IMPACT) was performed that included tumor samples from 38,468 individuals across all cancer types. Somatic variations were annotated using a precision knowledge (OncoKB) and available data stratified by level evidence. Alterations associated response...
You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II (PD51)1 May 2024PD51-03 CONNEXIN-26 EXPRESSION IS ASSOCIATED WITH DISEASE OUTCOMES IN CLEAR CELL RENAL CARCINOMA AND MAY BE A SOURCE OF INTRATUMORAL ADENOSINE Elizabeth Ellis, A. Ari Hakimi, Fengshen Kuo, and Phillip Rappold EllisElizabeth Ellis , HakimiA. Hakimi KuoFengshen Kuo RappoldPhillip View All Author Informationhttps://doi.org/10.1097/01.JU.0001009360.84490.42.03AboutPDF ToolsAdd to favoritesDownload...
Transmembrane protein 27 (TMEM27/collectrin), a glycoprotein and homolog of angiotensin-converting enzyme 2 (ACE2), is regulator renal amino acid uptake in the proximal tubule may have protective role hypertension. Two previous reports shown that absence TMEM27 expression clear cell carcinoma (ccRCC) correlates with poorer cancer-related survival. We report our findings ccRCC clinical outcomes an independent third cohort.We conducted retrospective analysis to identify all 321 cases diagnosed...
Abstract Background Intratumoral heterogeneity (ITH) is a hallmark of clear cell renal carcinoma (ccRCC) that reflects the trajectory evolution and influences clinical prognosis. Here we seek to elucidate how ITH tumor during immune checkpoint inhibitor (ICI) treatment can lead therapy resistance. Methods Here, spatiotemporally profiled genomic immunophenotypic characteristics 29 ccRCC patients, including pre- post-therapy samples from 17 ICI treated patients. Deep multi-regional whole exome...
You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP39)1 Sep 2021MP39-09 GENOMIC CHARACTERIZATION OF AGGRESSIVE SPORADIC EPITHELIOID ANGIOMYOLIPOMA Phillip M Rappold, Mark Zucker, Angela Yoo, Benjamin Davelman, Kate Weiss, Paul Russo, Jonathan Coleman, Martin H Voss, Timothy A Chan, Robert J Motzer, Yingbei Chen, Ed Reznik, Satish K Tickoo, and Ari Hakimi RappoldPhillip Rappold More articles by this author , ZuckerMark Zucker YooAngela Yoo DavelmanBenjamin...