# Role of SLIT-ROBO and MT1-MMP in MSC-Mediated Neovascularization

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $169,560

## Abstract

PROJECT SUMMARY
This is an application for a K08 Mentored Clinical Scientist Career Development Award to train Dr. Ming-Sing Si,
an Assistant Professor in Cardiac Surgery. Dr. Si has a strong interest in scientific investigation, as demonstrated
by his long track record of participation in research throughout every stage of his educational career. Dr. Si’s
Department has guaranteed him protected time, laboratory space, personnel support, and all other resources
required to complete this training program successfully. The proposed training program will provide Dr. Si the
necessary skills to become a successful independent investigator focused on mesenchymal stem cell (MSC)
and perivascular cell biology. Key components of the training will include graduate level courses in advanced
experimental methods, tissue regeneration, and responsible conduct of research, incorporation of advanced
genetic methods and novel transgenic mouse models in experimental design, frequent scheduled interactions
with his mentorship committee members, seminar and conference participation, manuscript writing, R01 grant
proposal writing, and basic science investigation into the function of MSC/perivascular cells in neovasculariza-
tion. The mentorship committee is comprised of three internationally renowned experts relevant to MSCs, sig-
naling, and angiogenesis. These experts are also experienced in providing mentorship to young clinicians and
scientists. The applicant has gathered preliminary data that implicate SLIT-ROBO signaling, a signaling axis for
axons and tip endothelial cells, in MSC behavior pertinent to neovascularization and tissue regeneration. Based
on these findings and related published results from one of his mentors on the importance of MT1-MMP and
Snail transcription factors in cell invasion, the applicant plans to define how, and to what extent, SLIT-ROBO
signaling and MT1-MMP stimulate MSC-mediated angiogenesis in vitro and in vivo, and to utilize this knowledge
to design novel therapeutic strategies that effectively stimulate neovascularization. The specific aims for this
project are: (1) Determine the effects of SLIT3-ROBO1 signaling on MSC motility, invasiveness, collagenolysis,
and angiogenesis in the setting of left ventricle (LV) pressure overload. (2) Define the role of the MT1-MMP on
MSC invasiveness MSC-mediated angiogenesis and heart failure. (3) Characterize the in vivo, native roles of
the perivascular mural cell-SLIT3-ROBO1 axis during LV pressure overload using conditional knockout mouse
models. This research will advance the understanding of angiogenic responses in the setting of multicellular
interactions and should provide valuable insights into the means by which therapeutic neovascularization can
be elicited. The completion of the proposed research and training plan will provide the knowledge and experience
for the applicant to become an independent investigator in the field of MSC biology, angiogenesis, and cardio-
vascular regener...

## Key facts

- **NIH application ID:** 10316213
- **Project number:** 5K08HL146351-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Ming-Sing Si
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $169,560
- **Award type:** 5
- **Project period:** 2020-12-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316213

## Citation

> US National Institutes of Health, RePORTER application 10316213, Role of SLIT-ROBO and MT1-MMP in MSC-Mediated Neovascularization (5K08HL146351-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10316213. Licensed CC0.

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