News
July 12, 2023
Congratulations Mohamed Haloul for passing his preliminary exam!!!
June 8, 2023
Congratulations Alexa Gajda for receiving the prestigious Bárány Student Award from the UIC College of Medicine, Department of Physiology and Biophysics for her hard work and conscientiousness!!
May 12, 2023
Our lab received a generous seed fund from the UI Cancer Centers' Community Outreach and Engagement Office's Hope Leaders Program! We will be working with community partners to share our research with the public and get their feedback.
April 28, 2023
Congratulations to Mohamed Haloul for winning the poster prize in Cancer Biology at the Gary Kruh Cancer Symposium organized by the UI Cancer Center!
April 19, 2023
We had a great time at the lab mixer events with breast cancer patients and patient advocates from the Sister Network. This was organized by the UI Cancer Center's Office of Community Engagement and Health Equity. Read the news here.
October 6, 2022
We just received an R37 MERIT grant from the NCI, A Conquer Cancer Now grant from the Concern Foundation. Read the story here: https://cancer.uillinois.edu/two-grants-one-paper-make-ers-month-unforgettable/ A big thank you to all our past and current members, colleagues, and collaborators for making these possible!
July 21, 2022
Congratulations to Alexa, who passed her preliminary qualifying exam! She is officially a PhD Candidate!
April 3, 2022
Emrah was selected as a NextGen Star by the American Association for Cancer Research. He will be giving a talk at the upcoming AACR Annual Conference on April 8-13, 2022. His talk will be during the Extracellular Matrix Remodeling in Cancer session.
February 22, 2022
Our work on mechanosurveillance was recently highlighted by Faculty Opinions, formerly known as F1000Prime. These add to other highlights we received from Cancer Discovery, Immunity, Nature Reviews Cancer, and Nature Reviews Immunology.
January 20, 2022
Er Lab received the Michael Reese Pioneer Research Award to investigate mechanobiology in metastasis!
August 26, 2021
Emrah's office moved to COMRB 1115.
March 22, 2021
Mechanosurveillance in metastasis is finally out! For open access to the published version at Immunity until May 11, 2021 click here. It is also available online through subscription here.
December 8, 2020
We welcome Alexa Gajda to our lab! She joined our lab as a graduate student with the GEMS program at UIC.
June 30, 2020
We welcome Keyvan and Kate to our lab! Keyvan is a postdoctoral fellow with bioengineering expertise and Kate is an MD/PhD student with the UIC MSTP program rotating in the Er Lab!
June 8, 2020
We are slowly reopening our lab according to IL state and UIC guidance. Welcome back to no longer virtual science!
April 23, 2020
We just uploaded our paper in review to BioRxiv! Our work shows describes the how mechanotransduction creates biophysical vulnerabilities in metastatic cells.
https://www.biorxiv.org/content/10.1101/2020.04.21.054304v1
April 22, 2020
Congratulations to Stephanie for the LASURI Award for her undergraduate research!
Mission
Cancer is a devastating disease that impacts the livelihood of patients and families worldwide. It is the second leading cause of death in the U.S. with limited number of therapeutic options for patients with advanced stage disease. Our research goal is to understand the fundamentals of cancer evolution and spread through out the body. We utilize animal models, innovative 3-dimensional cell culture and ex vivo organ culture methods, frequently use state-of-art microscopy, traditional molecular biology and biochemistry along with patient data driven bioinformatics and transcriptional profiling approaches to gain exciting new perspective into the biology of cancer. Through our own work and multi-institutional collaborations, we strive to answer the most pressing questions in cancer biology with the hope of inspiring novel therapies.
Significance
Cancer is a disease of uncontrolled cellular growth and replication, which disrupts the bodily function of the tissue in which it emerges. Even when cancerous tissues are successfully removed from the body, cancer cells can escape the diseased tissue and spread beyond their primary organ of origin. Cancer spreading to different secondary organs is called metastasis. Metastases account for the vast majority of cancer related deaths and unfortunately most of the treatments we have today are palliative.Metastasis accounts for the vast majority of cancer related deaths.
Metastasis is a complicated multi-step process with various molecular and cellular players acting at distinct steps of the cascade. First, cancer cells invade the tissue surrounding them, then enter into blood circulation, travel throughout the body using the vasculature, and exit the bloodstream at secondary organs. At this new microenvironment, disseminated cancer cells can stay dormant - meaning clinically silent- for months to decades or can immediately initiate colonization. Fortunately, the metastatic cascade is extremely inefficient: a lot of disseminated cancer cells that arrive at a new destination either get eliminated by immune cells or perish because they cannot adapt to their new microenvironment before they form clinically meaningful metastatic colonies. However, once metastatic colonies (metastases) arise, they are overwhelmingly challenging to treat. That’s why we focus on answering this central question in cancer biology: How do disseminated cancer cells grow into lethal metastatic colonies?
How do disseminated cancer cells grow into lethal metastatic colonies?
Our Focus
Fundamental biological processes that cancer cells utilize for metastasis, such as migration, adhesion and invasion, require these cells to dynamically control their cytoskeleton. Cytoskeleton is quite literally the skeleton of the cell. It is a collective of proteins that give cells their shape and their rigidity and is frequently reorganized based on environmental cues. However, cytoskeleton is not just the scaffold that the cells are built on; it is a physically pliable network that flows information about the cells’ surroundings to its core – the nucleus. Conventionally the role of cytoskeleton in metastasis has been thought to be important for the early steps of metastasis such as migration out of the primary organ, entry into blood circulation and exit out of the blood vessels. Cytoskeleton is not just the scaffold that the cells are built on; it is a physically pliable network that flows information about the cells’ surroundings to its core – the nucleus.
Recent evidence from our lab and others now brings an unprecedented appreciation of the role of cytoskeleton during the clinically meaningful stages of metastatic colonization. These are awakening of disseminated cancer cells from metastatic dormancy and outgrowth metastatic colonies in vital secondary organs. Upon arrival at secondary organs, disseminated cancer cells have the ability to sense and respond to the extracellular matrix, which is composed of structural proteins outside of cells and holds tissues together. Once the appropriate configuration of molecules that connect the extracellular matrix to cells’ surface is established, the cytoskeleton relays this information to the cancer cells’ nucleus.
The relay of information happens through cytoskeleton mediated activation of transcription factors, which bind to DNA at cells’ nucleus. Transcription factor binding to DNA profoundly alters protein production according to the cells’ needs. Cytoskeleton proteins can directly bind transcription factors, sequester them away from their position of activity or facilitate their localization into the nucleus. The decisions made at the transcription factor level critically affect what will happen to disseminated cancer cells in the longer run: will cancer cells be effectively destroyed, enter prolonged dormancy or resume colonization?
The decisions made at the transcription factor level critically affect what will happen to disseminated cancer cells in the long run: will cancer cells be effectively destroyed, enter prolonged dormancy or resume colonization?
The interactions between the cancer cells, the extracellular matrix, the vasculature and the immune system do not only happen in the form of molecular communication between proteins. There is abundant evidence suggesting that the physical context of these interactions are critical for determining biological outcomes resulting from these interactions. Cellular and tissue stiffness, rigidity, compliance, shear stress and fluid pressure are all physical (more precisely biophysical) contexts. These biophysical parameters can be drastically different between the cancer cells’ primary organ of origin and the new secondary organs they disseminate. These biophysical parameters all contribute to the behavior of the disseminated cancer cells and determine how effectively they can be eliminated or whether they will grow into lethal colonies.
Biophysical parameters critically contribute to metastatic outgrowth.
Our Approach
The important observations that metastases are composed of both biochemical and biophysical constituents form the foundation of our research program. Our goal is to bring a systems biology approach to studying cancer metastasis. By systems biology, we do not only mean the genetic and molecular heterogeneity of cancer cells and the cells in the cancer microenvironment, but also the physical environment they reside in and travel through. We use immunocompetent mouse models of metastasis in vivo, mouse and human cancer cell lines both in xenografts in vivo and in tissue culture settings in vitro, use ex vivo brain slice culture models, gravity induced 3-dimensional models of tumor growth and artificially induced vascular organization experiments as well as co-culture models of cancer cells, vascular cells and immune cells. We have extensive expertise in animal modeling but always welcome new sophisticated technologies that allow us to closely model human cancer more as alternatives to animal modeling. We routinely perform transcriptional profiling, traditional protein biochemistry, high-end confocal, bright field and time-lapse microscopy, as well as molecular biology to engineer novel genetic tools to study cancer biology and also are gearing towards performing single cell RNA sequencing. Through our collaborations we seek to use atomic force microscopy to measure cellular stiffness and generate physically defined extracellular environments to understand the molecular basis of metastasis. By studying all the biophysical and biochemical inputs into cellular decision making, we are aiming to bring an interdisciplinary approach to understanding the metastatic process.
We are aiming to bring an interdisciplinary approach to understanding the metastatic process.