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A postdoctoral fellow position is available immediately to lead studies on a newly defined metabolic-immune circuit that drives resistance to immune checkpoint inhibitors (ICI) in melanoma. The project builds on our finding that ICI-induced inflammation (IL-6/IFN- to TOPK to HECTD1) accelerates hepatic PAH degradation, raising systemic phenylalanine (Phe), which then engages a neutrophil GRIK1-CaMKIV-STING-type I IFN program that drives CD8+ T cell exhaustion. The fellow will test two clinically compatible interventions: hepatocyte-targeted HULC RNA mimetics that stabilize PAH, and repurposed topiramate, an FDA-approved GRIK1 inhibitor, that blocks neutrophil Phe sensing.

This work spans genetically engineered and humanized (huCD34-MISTRG) mouse models, patient-derived melanoma models, hiPSC-derived hepatocytes, RNA therapeutic delivery, multiplex spatial proteomics, and a 562-patient clinically annotated cohort. The project is supported by an established team of co-investigators in ICI and T cell biology, neutrophil biology, dermatopathology, clinical melanoma, biostatistics, and nanomedicine. All duties and responsibilities are carried out in compliance with institutional policies, ethical research standards, and applicable federal and state regulations.

LEARNING OBJECTIVES Design and execute in vivo studies in huCD34 humanized mice engrafted with melanoma patient-derived cell (PDC) models under defined dietary Phe regimens and ICI treatment. Breed, genotype, and phenotype compound genetic models, including BrafCA/+;PtenloxP/loxP;Tyr::CreERT2, PahR408W, and neutrophil-specific Grik1f/f; Mrp8-Cre lines. Isolate and profile tumor-associated neutrophils and tumor-infiltrating CD8+ T cells by flow and phospho-flow cytometry, CyTOF, ELISA, Seahorse extracellular flux, and cytotoxicity assays.

Dissect the PAH degradation pathway and the GRIK1-CaMKIV-STING axis using immunoprecipitation, ubiquitination and phospho-specific immunoblotting, in vitro kinase assays, CRISPR/Cas9 editing, and hiPSC-derived hepatocyte and neutrophil-like cell systems. Formulate, deliver, and evaluate GalNAc-conjugated and LNP-encapsulated HULC RNA mimetics, including pharmacokinetics, biodistribution, and toxicity studies. Perform and analyze COMET multiplex spatial proteomics on murine and human melanoma tissue and integrate results with bulk RNA-seq and scRNA-seq datasets.

Prepare manuscripts, present at national meetings, and contribute to grant applications, including fellowship and career development awards. ELIGIBILITY REQUIREMENTS PhD, MD, or MD/PhD, or expected within six months, in immunology, cancer biology, molecular biology, biochemistry, pharmacology, or a related discipline. Demonstrated productivity, evidenced by at least one first-author publication in a peer-reviewed journal.

Hands-on in vivo experience: syngeneic and/or xenograft tumor implantation, tumor growth monitoring, survival studies, mouse colony management, genotyping, and IACUC protocol compliance. Multicolor flow cytometry, including immune panel design, tissue dissociation, and analysis of tumor-infiltrating lymphoid and myeloid populations. Core molecular and biochemical techniques: immunoblotting, co-immunoprecipitation, qRT-PCR, ELISA, plasmid and lentiviral construct generation, CRISPR/Cas9 gene editing, and primary cell culture.

Quantitative rigor: appropriate statistical testing, power considerations, blinding and randomization, and transparent record keeping. Strong written and spoken English, with the ability to work independently and within a multidisciplinary collaborative team. POSITION INFORMATION MD Anderson offers full-time postdoc positions with a salary ranging from $64,000 to $76,000.

depending on the number of years of postgraduate experience. The University of Texas MD Anderson Cancer Center offers excellent benefits, including medical, dental, paid time off, retirement, tuition benefits, educational opportunities, and individual and team recognition Offsite work arrangements are subject to approval and may be modified or revoked at any time based on business needs, performance considerations, or regulatory requirements. This position may be responsible for maintaining the security and integrity of critical infrastructure, as defined in Section 113.001(2) of the Texas Business and Commerce Code and therefore may require routine reviews and screening

The ability to satisfy and maintain all requirements necessary to ensure the continued security and integrity of such infrastructure is a condition of hire and continued employment. It is the policy of The University of Texas MD Anderson Cancer Center to provide equal employment opportunity without regard to race, color, religion, age, national origin, sex, gender, sexual orientation, gender identity/expression, disability, protected veteran status, genetic information, or any other basis protected by institutional policy or by federal, state or local laws unless such distinction is required by law. http://www.mdanderson.org/about-us/legal-and-policy/legal-statements/eeo-affirmative-action.html Apply