# Molecular Drivers of Elevated Gallbladder Cancer Incidence in New Mexico

> **NIH NIH P20** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $265,125

## Abstract

Project Summary:
 Gallbladder Cancer (GBC) is the fifth most common malignancy of the GI tract and the most common in
the human biliary tree. Approximately 4,000-5,000 new cases of GBC are diagnosed in the United States
annually. Survival outcomes are dismal with only ~8% 5-year survival rate, making it one of the deadliest
cancers. GBC has a distinct geographical incidence pattern with global hotspots. These hotspots include
countries like Chile, Bolivia, India and the state of New Mexico (NM) in the United States. GBC incidence is
abnormally high among the “minority-majority” Native Americans (5-8 fold higher) and Hispanics (2-4 fold
higher) compared to Caucasians living in New Mexico. The reasons underlying GBC incidence disparities in
NM is unknown and there are critical gaps in our understanding of gallbladder carcinogenesis.
 We postulate environmental heavy metal exposure is the key risk factor responsible for GBC disparities
seen among minorities of NM. The southwestern United States (NM, AZ, UT and NV) has a long environmental
legacy of abandoned heavy metal mines. These mines are usually found in close proximity to a significant
number of socio-economically disadvantaged Native American and Hispanic communities of NM. To prove our
GBC hypothesis, we propose the use of New Mexican patient derived gallbladder epithelial cell lines in this
proposal. Aim 1 will use post-surgical gallbladder samples to determine the somatic mutational landscapes and
key molecular drivers of GBC in an ethnicity and gender dependent manner. Aim 2 will determine the impact of
exposures of two metals of significance in New Mexico, uranium and cadmium, on the GB phosphoproteomic
cell signaling dysregulation. In particular, we will focus on the role of metal exposure driven PI3K-Akt and
MAPK signaling pathway alterations. Aim 3 will determine the effects of cadmium and uranium exposure on
gallbladder epithelial barrier disruption and wound healing as a mechanistic explanation of GBC disparities
seen in NM. Aim 3 will confirm, for the first time, the role of metal induced disruption of the GB epithelial barrier
causing chronic transmural inflammation which is a well-known prerequisite of gallbladder carcinogenesis.
 Our long-term goal is to understand the molecular mechanisms of gallbladder carcinogenesis using
innovative, high-throughput bioinformatics approaches. This basic science proposal deeply informs the
translational clinical initiatives currently underway in our lab. Finally, this proposal will also provide a firm
scientific basis to enable preventative, population based screening measures to alleviate GBC disparities seen
in Native American and Hispanic communities of New Mexico.

## Key facts

- **NIH application ID:** 9854033
- **Project number:** 1P20GM130422-01A1
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Rama Gullapalli
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $265,125
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854033

## Citation

> US National Institutes of Health, RePORTER application 9854033, Molecular Drivers of Elevated Gallbladder Cancer Incidence in New Mexico (1P20GM130422-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9854033. Licensed CC0.

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