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Secreted peptides as biomarkers and effectors of neuroendocrine transformation

Award Number: K22CA303784
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Secreted peptides as biomarkers and effectors of neuroendocrine transformation - ABSTRACT Most lung cancers are thought to develop from specialized secretory cells. For example, lung adenocarcinoma (LUAD) is suspected to develop from surfactant protein producing alveolar epithelial cell types and small cell lung cancer (SCLC) from pulmonary neuroendocrine cells (PNECs). PNEC biology is poorly understood, partially due the rarity of these cells. SCLC is a challenge to detect in the early stage and efforts to screen heavy smokers with low dose CT imaging has not improved detection. While most SCLC is associated with a history of cigarette tobacco smoking, cases of histological transformation of LUAD to SCLC are increasingly noted following treatment with targeted therapy. I recently described a genetically engineered mouse model capable of undergoing LUAD-to-SCLC transformation and applied single cell sequencing approaches to characterize the transition between LUAD and SCLC. Using this isogenic system to model independent histologic types of lung cancer, I was struck by the differing developmental kinetics. Where LUAD developed progressively, SCLC developed rapidly, after a prolonged period of smoldering tumorigenesis. It was unclear whether these differences were rooted in cell intrinsic or extrinsic features. To interrogate these differences, I propose to chart tumor ligand – immune cell interactions over time and space in Aim 1 of my proposal using newly developed single cell approaches, in collaboration with computational biologists at Weill Cornell Medicine. In Aim 2, I will use new mouse models of neuroendocrine transformation to capture tumor-derived ligands shed throughout tumorigenesis. Using click-chemistry enrichment and mass spectrometry-based characterization of secreted factors from transformed PNECs, I will deeply characterize the transformed “secretome.” Then, using CRISPR/Cas9-based gene disruption, I will study the effects of inactivating specific tumor ligands on the intrinsic and extrinsic control of lung tumorigenesis. Finally, in collaboration with several clinical colleagues, my third Aim will determine whether the neurotrophic cytokine pleiotrophin has relevance as a SCLC-specific biomarker and can extend to other neuroendocrine cancers. This proposal builds upon on the results generated during my postdoctoral training and will serve as my laboratory's focus during the start of my independent group. My background in lung cancer biology and therapeutic development during graduate school combined with my deep expertise in developmental mouse models of tumorigenesis and single cell genomics gained during my postdoctoral training, help position me for a successful transition to independence. As part of this award, I will assemble an advisory team at my institution to support my transition and career development training activities outlined herein. My outlined training plan will continue my development as an independent investigator, strengthen my collaborative networks and advance my expertise in lung cancer biology, including exciting new directions for the early detection of aggressive neuroendocrine cancers.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $192,224 )
2026	2026	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Research Manpower	000	1	8/5/2026	NEW	$192,224
														Subtotal = $192,224

Grand Total All Awards = $192,224

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Secreted peptides as biomarkers and effectors of neuroendocrine transformation

Award Number: K22CA303784

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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