# Targeting SOCS1 and RASA2 to Engineer More Potent Adoptive T Cell Therapies for Cancer Treatment.

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $263,267

## Abstract

The goal of this K08 application is to provide Dr. Julia Carnevale, MD, with the skills she will 
need to become an independently-funded laboratory investigator studying novel ways to engineer T 
cells with more potent anti-tumor activity. There is intense clinical interest in improving 
adoptive T cell therapies to treat and cure more cancers. However, until recently there has been no 
way to efficiently and comprehensively evaluate the genome to find the critical gene networks that 
can be leveraged to program favorable human T cell behaviors. Dr. Carnevale recently developed a 
novel screening technology, sgRNA lentiviral infection with CAS9 electroporation (SLICE), that 
enables genome-wide CRISPR screening in primary human T cells to search for genes that regulate key 
therapeutic functions. Dr. Carnevale used SLICE to perform a genome-wide screen in T cells which 
identified a host of regulators of proliferation, many of which also enhanced T cell activation and 
in vitro cancer cell killing. She now proposes targeting top-raking genes from this screen, SOCS1 
and RASA2 (negative regulators of JAK/STAT and MAP kinase signaling, respectively), to improve the 
efficacy of adoptive T cell therapies. She hypothesizes that disruption of SOCS1 or RASA2 will 
enhance the anti-tumor properties of human T cells, that these genes can be targeted to improve 
adoptive T cell therapies, and that SLICE pooled screening can be performed in vivo to identify 
modifier gene targets that synergize with SOCS1 and RASA2 loss to improve tumor control. The 
specific aims of the proposed research are: 1) to test how SOCS1 and RASA2 influence T-cell 
responses  to  repeated  stimulation  and  explore  the  molecular  pathways  that  govern  these  
responses,  2)  to determine the effects of SOCS1 or RASA2 inactivation on antitumor activities of 
T cells in vivo, and 3) to identify gene targets that synergize with SOCS1 or RASA2 loss in vivo. 
Dr. Carnevale's training and research plans includes a combination of structured coursework and 
workshops, one-on-one tutorials, and hands-on research experience  that  will  all  take  place  at 
 UCSF,  a  world-renowned  academic  center  of  excellence  in  basic  and translational research. 
Dr. Carnevale's training plan will complement her existing expertise to build a strong foundation 
in the following areas: 1) fundamental T cell biology including the study of regulatory circuitry, 
function, and tumor immunity, 2) preclinical modeling of adoptive T cell therapies, and 3) 
next-generation sequencing methods and analysis including single-cell RNA sequencing. This project 
will be conducted under the mentorship of her primary mentor, Dr. Alan Ashworth, President of the 
UCSF Cancer Center and world expert in therapeutic discovery and translational research, and her 
co-mentor, Dr. Alex Marson, leading expert in genome engineering in immune cells. She will also 
receive extensive input from her distinguished advisory p...

## Key facts

- **NIH application ID:** 10656342
- **Project number:** 5K08CA252605-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Julia C Carnevale
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $263,267
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656342

## Citation

> US National Institutes of Health, RePORTER application 10656342, Targeting SOCS1 and RASA2 to Engineer More Potent Adoptive T Cell Therapies for Cancer Treatment. (5K08CA252605-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10656342. Licensed CC0.

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