Cancer Biology and Cell Signaling Program

Program Description:

Dysregulation of cell signaling is one of the major mechanisms resulting in the development, progression, relapse of cancer, as well as the development of drug resistance in tumors.  With the combined research efforts of the Signaling, Stem Cell and Experimental Therapeutics faculty, we want to identify the key pathogenic signaling pathways involved in cancer and elucidate the underlying cellular/molecular mechanisms.  We intend to identify novel and less toxic medications to better treat cancer.

Program Directors:

Basic Science Research:  Jiwang Zhang, MD, PhD
Associate Professor of Pathology
Oncology Research Institute

Clinical Research: Patrick J. Stiff, MD
Professor of Medicine (Hematology/Oncology)

Program Goals:

  1. Abnormal activation of proliferative and survival signaling and inactivation of differentiation signaling due to genetic mutations of key regulators/mediators of these signaling pathways and/or aberrant stimulation emanating from tissue microenvironments are the essential drivers for most types of cancers.  We are interested in identifying such driver signaling pathways and elucidate how they stimulate cancer development and progression.  In doing so, we intend to be in position to identify novel targeted therapies for various types of cancer.
  2. Disease relapse owing to minimal residual disease and drug-resistance are the critical problems that impair the success of current cancer therapies.  We are interested in understanding how cancer cells escape the intended effects of anti-neoplastic agents.  We also want to develop combination treatments to eliminate these “escapers”.   
  3. We want to promote and work toward greater expertise in stem cell differentiation and reprograming.  We believe that in addition to self-renewal, dedifferentiation is one of the key mechanisms of cancer stem cell propagation and drug resistance.  We are interested in uncovering and exploring critical factors which can induce cancer stem cell differentiation and/or repress cancer cell dedifferentiation.  

Scientific Goals:

  1. Determine the driver signals for cancer progression, relapse and drug-resistance.
  2. Understand the regulatory mechanisms governing self-renewal and dedifferentiation of normal tissue stem cells, pre-cancer stem cells and cancer stem cells.
  3. Determine the signaling factors emanating from tissue micro-environments (niches) which help to stimulate self-renewal and dedifferentiation to cancer cells.


Jiwang Zhang, MD, PhD
Department of Pathology/Oncology Research Institute

Stem cells are a key subset of cells in the body that function as ancestor cells to produce a variety of types of functionally specialized mature cells in a given tissue, while at the same time maintaining the capacity of self-renewal. Self-renewal of stem cells is a process of continuous division to reproduce themselves. This process is controlled by intrinsic genetic pathways that are subject to regulation by extrinsic signals from the microenvironment in which stem cells reside. Stem cell development is a complex process and is maintained precisely in balance among different cell events including self-renewal, differentiation, apoptosis, and migration. Breaking this balance tends to lead to either lack of or uncontrolled cell growth, thereby developing into a variety of diseases including tissue defects and cancers.

Hematopoietic stem cells (HSCs) play essential roles in hematopoietic tissue homeostasis and regeneration. Leukemia stem cells (LSCs) are the subset of malignant cells in leukemia patients which are the initiators of leukemia development and are also the resources of leukemia relapse. Like normal stem cells, LSCs have self-renewal capacity. LSCs derived either from normal HSCs that obtained malignant properties without losing self-renewal ability or mutant progenitors which gained the self-renewal feature. Therefore, LSCs are the key targets for clinical leukemia therapy. The overall objectives of our research are: 1. to investigate the cellular and molecular mechanisms that regulate bone marrow HSC self-renewal, proliferation and differentiation and the interaction between stem cells and their microenvironment; 2. to investigate the LSC and leukemia development by using genetically modulated mouse models. This study is important to enhance our understanding of the nature of stem cells and leukemia development. It will help to identify cellular components and molecules that are important for in vitro expansion of HSC, which could be used for clinical therapies. Additionally, it will provide insights of the difference in molecular regulations of LSC and normal HSC which would lead to the discovery of specific targets for destroying the LSCs without affecting the normal HSCs.

 

Wei Qiu, PhD
Assistant Professor
Department of Surgery/Oncology Research Institute
http://weiqiu-lab.weebly.com/

Dr. Qiu received his PhD from the Institute of Zoology, Chinese Academic science in 2005. He continued his training as a postdoctoral fellow at the University of Pittsburgh Cancer Institute in the laboratory of Dr. Jian Yu, working on molecular mechanisms of cell death and tumorigenesis. In 2012 he joined the Stem Cell Biology Program at the Oncology Institute at Loyola University Chicago as Assistant Professor.

Dr. Qiu’s current primary research interest is to study signaling pathways of steatohepatitis, hepatic fibrosis and hepatocellular carcinoma. He is also interested in regulation of hepatic stem cell self-renewal and differentiation. He has proven himself as a productive scientist by publishing 27 peer-reviewed papers in high quality journals, including Cell Stem Cell, JCI, PNAS, Hepatology, Cancer Research, and Oncogene.

A wide variety of approaches are employed in Dr. Qiu’s studies, including molecular and cell biology techniques, state-of-art cell imaging, transgenic and knockout mouse models, injury and cancer models, and correlative studies using clinical samples.