Julio A Aguirre-Ghiso, PhD
img_Julio A Aguirre-Ghiso
ADJUNCT PROFESSOR | Medicine, Hematology and Medical Oncology
Research Topics
Autophagy, Cancer, Cell Adhesion, Cell Motility, Extracellular Matrix, Gene Expressions, Gene Regulation, Integrins, Metastasis, Morphogenesis, Oncogenes, Signal Transduction, Stem Cells, Tumorigenesis
Multi-Disciplinary Training Area
Cancer Biology [CAB]
Current Students: Kathryn Harper, Miguel Vizarreta Sandoval Postdoctoral Fellows: Maria Soledad Sosa, Georg Fleugen, Veronica Calvo Vidal, Nina Linde Research Personnel: Julie Cheung Lab Administrator: Jolanda Mernacej Overview Surprisingly cancer patients presumed cured can carry non-proliferating ‘dormant’ disseminated tumor cells (DTCs) for years before they activate to form incurable metastasis. We focused on understanding the biology of dormant DTCs to target them and prevent relapse. This contrasts to the vast majority of cancer research, which focuses on understanding constant cancer growth. My team led a paradigm shift that is revealing novel cancer biology. By a multidisciplinary approach integrating mechanisms of basic stress and mitogenic signaling, adult stem cell, intra-vital imaging and micro-environmental biology, we discovered that reciprocal crosstalk between DTCs and the microenvironment regulates the inter-conversion between dormancy and proliferation. A major achievement of my team was discovering that imbalance in p38 and ERK1/2 signaling regulates lineage commitment transcription factor (TF) networks determining dormancy induction. I also identified retinoic acid and TGF2 in the microenvironment as inducers of the high p38/ERK signaling ratio and that dormancy (quiescent phenotype) is controlled by mechanisms driving adult and embryonic stem cell biology. Translating this biology to medicine we identified a “dormancy signature” enriched in dormant DTCs from patients asymptomatic for >10 years, predicting prolonged metastasis-free periods in different cancers. Our work has propelled new questions to the forefront of cancer research, with the unexpected discovery of the mechanisms that regulate early dissemination and that dormant DTCs can originate very early during cancer evolution, disseminating during pre-malignant stages of cancer. My team has also studied the role of endoplasmic reticulum stress signaling in tissue morphogenesis and DTC biology and we discovered that UPR signaling can promote the survival of dormant tumor cells. We also study how UPR signaling triggered by therapies in multiple myeloma can induce residual disease dormancy and how can we target these residual cancer cell. We have also studied the role of host cells specifically macrophages in regulating early dissemination and DTC fate. We found that macrophages are key players in the regulation of early dissemination and dormancy. My lab is part of a NCI-Tumor Microenvironment Network Center along with Einstein (John Condeelis), Univ. Of Wisconsin (Patricia Keely) and the College of Nanoscale Sciences (James Castracane). This Center studies the role of microenvironmental stress and dormancy and the development of new technologies to image and target metastasis. My lab also collaborates with Christoph Klein’s lab (Univ. of Regensburg), Nicholas Steocklein (Univ. of Duddeldorf) and Colm Morrissey’s lab at the University Of Washington, to characterize dormancy in human DTCs. We also collaborate with Dr. Emily Bersntein, an expert in melanoma epigenetics on the epigenetic regulation of DTC dormancy, among others. This translational focus is strengthened by my roles in clinical programs and as Research Leader of the Metastasis Center at Mount Sinai. Our lab has a long term interest in translational efforts and we have thus developed a pre-clinical and translational program in with Eli Lilly to identify drugs to target dormant disease. This multidisciplinary program has allowed us to develop basic mechanistic work, but also translational research on DTC biology and metastasis, which has an important impact in our understanding of cancer biology.

MSc, University of Buenos Aires

PhD, University of Buenos Aires

Charles Revson Foundation

The Mount Sinai School of Medicine

2014

Co-Chair, Plenary Lecture Session

2nd Advances in Circulating Tumour Cells Meeting

2014

Editorial Board

International Journal of Stem Cell Research

2013

Advisor

The National Breast Cancer Coalition Artemis Project on Breast Cancer Dormancy

2012

Speaker and Chair

Princess Takamatsu Cancer Research Symposium

2012

Speaker

Herrenhausen Symposium on Metastasis, Nature Medicine Kloster

2012

Co-Chair

Plenary Lecture Session, 1st Advances in Circulating Tumour Cells Meeting

2012

Speaker Symposium

AACR Meeting: Dormant and Stem Cells in Tumor Heterogeneity

Editorial Board of Cancer Research, Breaking Advances Editor

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Below are financial relationships with industry reported by Dr. Aguirre-Ghiso during 2022 and/or 2023. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Company Founder:

  • HiberCell LLC

Consulting:

  • HiberCell LLC

Equity (Stock or stock options valued at greater than 5% ownership of a publicly traded company or equity of any value in a privately held company)

  • HiberCell LLC

Other activities: Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership

  • HiberCell LLC

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.