# Core B – Human Biospecimen and Advanced Sequencing Core

> **NIH NIH P01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $210,973

## Abstract

PROJECT SUMMARY: CORE B
The goal of this Program is to advance knowledge of pancreatic ductal adenocarcinoma (PDAC), a recalcitrant
cancer with one of the highest rates of cachexia. Project 1 focuses on PDAC-induced circulating factors, including
IL-6 and its soluble receptor (sIL6R), leading to wasting of the target tissues via activation of STAT3 and NF-kB
in adipocytes and myofibers. Project 2 investigates IL-6 and NF-kB in the skeletal muscle microenvironment in
PDAC cachexia, as well as NF-kB in the tumor microenvironment and its effects on macrophages. Project 3’s
studies probe interactions of IL-6, STAT3, and NF-kB among tumor cells, fibroblasts, and macrophages in the
tumor microenvironment. Together these studies will tackle both PDAC tumor biology and the metabolic havoc
it creates for the patient. Core B will provide the Projects with unprecedented potential to interrogate the PDAC
macroenvironment by providing 1) human clinical specimens to evaluate the translational potential of their
findings, and 2) the capacity to carry out transcriptome profiling at the single cell level using single cell and single
nucleus RNAseq in matched samples from patients with PDAC, and 3) dedicated support for advanced sequence
analysis. In doing so, this Core addresses barriers that have historically limited research in PDAC and cancer
cachexia. Very few studies have reported gene expression or histological endpoints in peripheral tissues in
human cancer cachexia and even fewer in PDAC cachexia, and none have attempted to match analyses across
tissues. As well, these pioneering studies at single cell resolution in the PDAC macroenvironment of mouse
models and humans, carried out by investigators at the forefront of these technologies and analytical capabilities
will enable the Projects to make groundbreaking discoveries while contributing novel, high resolution data to the
field. The specific aims are to 1) Collect, store and distribute clinically annotated PDAC cachexia
biospecimens. Clinical data and biospecimens will be collected from PDAC surgical patients at Indiana
University Simon Comprehensive Cancer Center (IUSCCC) and from patients from the Danish PACTO Trial for
centralized compliance, processing, and distribution. 2) Carry out a single nucleus (sn) RNAseq study of the
human PDAC cachexia macroenvironment for all Projects. Muscle and adipose samples from IUSM general
surgery patients with benign conditions and muscle, adipose and tumor samples from IUSCCC PDAC surgery
patients with and without moderate cachexia will be processed to make single nuclei preparations. Batched
samples will be subjected to snRNAseq to test specific hypotheses for each of Projects 1-3 and the overall
program. 3) Provide advanced analysis of single cell (sc) and snRNAseq studies for all Projects. Core B
will provide dedicated advanced analysis of the snRNAseq data from human specimens in Aim 2 for Projects 1-
3, and of sn or scRNAseq data from mice emanating from eac...

## Key facts

- **NIH application ID:** 10898584
- **Project number:** 5P01CA236778-04
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** LEONIDAS G. KONIARIS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $210,973
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898584

## Citation

> US National Institutes of Health, RePORTER application 10898584, Core B – Human Biospecimen and Advanced Sequencing Core (5P01CA236778-04). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10898584. Licensed CC0.

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