Northwestern University Feinberg School of Medicine
Department of Pharmacology
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Cancer Pharmacology

Cancer pharmacology is the study of the molecular and cellular mechanisms of cancer cells and the identification of novel therapeutic targets and treatment strategies. Faculty in the department study basic mechanisms responsible for cancer and its spread (metastasis) with the goal of finding new molecular targets for destroying cancer cells. An emphasis on difficult to treat breast cancer subtypes, which includes research on cancer stem cells, is leading to discoveries of new disease mechanisms and drug targets.

Our Work

Cancer Causes Research

Investigating the Root Cause of Cancer

Huiping Liu, MD, PhD, associate professor of Pharmacology, studies cancer stem cells and how they can be used to create new therapies that eradicate the root cause of cancers.

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Cancer Pharmacology Research Labs

 Paul Burridge Lab

Investigating the application of human induced pluripotent stem cells to study the pharmacogenomics of chemotherapy off-target toxicity and efficacy

Research Description

The Burridge lab studies the role of the genome in influencing drug responses, known as pharmacogenomics or personalized medicine. Our major model is human induced pluripotent stem cells (hiPSC), generated from patient's blood or skin. We use a combination of next generation sequencing, automation and robotics, high-throughput drug screening, high-content imaging, tissue engineering, electrophysiological and physiological testing to better understand the mechanisms of drug response and action.

Our major effort has been related to patient-specific responses to chemotherapy agents. We ask the question: what is the genetic reason why some patients have a minimal side effects to their cancer treatment, whilst others have encounter highly detrimental side-effects? These side-effects  can include cardiomyopathy (heart failure or arrhythmias), peripheral neuropathy,  or hepatotoxicity (liver failure). It is our aim to add to risk-based screening by functionally validating genetic changes that predispose a patient to a specific drug response.

Recent Findings

  • Human induced pluripotent stem cells predict breast cancer patients’ predilection to doxorubicin-induced cardiotoxicity
  • Chemically defined generation of human cardiomyocytes

Current Projects

  • Modeling the role of the genome in doxorubicin-induced cardiotoxicity using hiPSC
  • Investigating the pharmacogenomics of tyrosine kinase inhibitor cardiotoxicity
  • hiPSC reprogramming, culture and differentiation techniques
  • High-throughput and high-content methodologies in hiPSC-based screening

For lab information and more, see Dr. Burridge’s faculty profile and lab website.

Publications

See Dr. Burridge's publications on PubMed.

Contact

Contact Dr. Burridge at 312-503-4895.

Lab Staff

Postdoctoral Fellows

Zhengxin Jiang, Tarek Mohamed, Adam Schuldt

Graduate Students

K. Ashley Fetterman, Michael Orman, Stewart Pine, Marisol Tejeda

Technical Staff

Defne Egecioglu, Hui-Hsuan Kuo

 Debabrata Chakravarti Lab

Transcriptional and Epigenetic Regulatory Mechanisms in Nuclear Hormone Signaling and Cancer Cell Function

Research Description

The Chakravarti laboratory is interested in understanding the roles of nuclear hormone signaling and epigenetic modifications in regulating normal cell and organ physiology and how altered transcriptional and epigenetic signaling contributes to cancer development and metastasis.  To pursue these overall goals, we are currently focusing on three research areas which are of significant current interests in biomedical field.

Research Area 1: Transcriptional Regulation of Tumor Development: Cancer is a complex disease and remains poorly understood. In particular, how altered transcriptional and epigenetic regulation contributes to cancer development and progression is not clear. We have recently discovered and characterized a new family of proteins termed the THAP family. Using xenograft mouse model, next generation mRNA and ChIP deep sequencing, extensive analysis of human progressive cancer tissue samples and state-of-the-art molecular techniques, members of the laboratory are determining the role of this novel THAP domain transcription factor and its cofactor HCF1 in cell cycle regulation and cancer progression. These studies should advance our knowledge of cancer progression and may provide a molecular target for therapeutic intervention.  

Research Area 2: Nuclear Hormone Receptor Signaling in Physiology and Uterine Fibrosis: Alterations of receptor/hormone function and coactivator and corepressor proteins have been implicated in several human diseases including cancer and fibrotic diseases.  We are currently determining the role of epigenetic changes and novel cofactors in hormone signaling and prostate and breast cancer. Tissue fibrosis is a major health problem in the world. We have profiled all 48 human nuclear receptors in uterine fibroids and found profound changes of receptor expression in normal and fibroid uterine tissues.  Laboratory members are currently using biochemical, bioinformatics, ChIP, deep sequencing and molecular techniques to determine epigenetic cross talk in hormone signaling and human cancer and uterine fibroids. 

Research Area 3: Epigenetic Modifications and Effectors of Chromatin Function: Combinatorial histone modifications including acetylation, methylation and phosphorylation play important regulatory roles in gene expression, chromatin function and cell cycle progression. We have recently demonstrated that the SR-proteins are critical cell cycle-dependent effector proteins for histone H3 serine 10 phosphorylation. We are also determining the role of histone H3 T11 phosphorylation and its effector protein WDR5 in androgen receptor function and in prostate cancer. Members in the laboratory are currently investigating the mechanisms by which these “effector-modification” interactions contribute to cell cycle progression and human diseases including cancer.

Chakravarti Lab Image

For more information, please see, visit the Dr. Chakravarti's faculty profile.

Publications

See Dr. Chakravarti's publications in PubMed.
Editorial Board:  Molecular Endocrinology 2011- present, Mol. Cell. Biol. 2014-2017
The Editor of a Book volume on “Regulatory Mechanisms in Transcriptional Signaling” in Progress in Molecular Biology and Translational Science (Vol 87), published in Aug 2009, Academic Press, Chakravarti, D. Editor

Staff Listing

Post-doctoral Fellows

J. Brandon Parker, Ph.D
Ji-Young Kim, Ph.D

Graduate Students

Aurimas Vinckevicius
Hanwei Yin
Mthabisi Moyo

Research Assistant

Sanjay Kottapalli

Contact Us

Dr. Chakravarti

Contact Chakravarti lab at 312-503-0782, 312-503-0783 or 312-503-0784. Our fax is 312-503-0095.

 David Gius Lab

Investigating of the mechanistic connection between aging, cellular and/or mitochondrial metabolism and carcinogenesis with specific focus on the Sirtuin gene family.

Research Description

Human sirtuins are the human homologs for the yeast and C. elegans longevity genes and breast cancers have one of the strongest correlations to age. Having this information, it is proposed that the primary sirtuin family knockout mice may present a novel group of models to establish, validate and investigate the well-established connection between aging, metabolism and cancer. To address this idea, over the past five years, we have constructed mice that have the three primary (Sirt1-3) sirtuins genetically deleted.

These each develop breast cancer, as well as other types of malignancies to varying degrees, and the levels of SIRT1-3 are also decreased in human cancer samples, as compared to normal tissues. In addition, the mechanism connecting the tumor permissive phenotype and the aberrant regulation of mitochondrial ROS, at least in part, in the Sirt3 knockout mouse has recently been published. Based on these results it seems clear that the primary sirtuin deacetylase proteins are tumor suppressor in several breast cancers as well as to a lesser extent in several other human malignancies.

Currently, our lab is utilizing the murine in vivo and in vitro models in several different projects examining the interactions of Sirt2 with proteins KRas, PKM2 and P53. We are also pursuing the efficacy of chemopreventive agents in luminal B breast malignancies. In addition we are studying the mechanistic link connecting Sirt2 and Sirt3 to cancers of the breast, pancreas, liver and lung. Finally, we have a group of neuroscientists examining the potential role of sirtuins in the development of neurodegenerative diseases that are associated with aging, particularly Parkinson’s.

For lab information and more, see David Gius', MD,PhD, faculty profile.

Publications

See Dr. Gius' publications in PubMed.

Contact Gius Lab

Contact the Gius Lab at 312-503-0332. You may also contact Dr. Gius directly at 312-503-2053 or via email.

Assistant Professors

Meejeon Roh, PhD/email

Lab Manager

Post-doctoral Fellows

Yueming Zhu, PhD

Graduate Students

Technical Staff

Marta Imbesi, PhD, Guoxiang Liu, PhD, Yufan Yan, BS

 Dai Horiuchi Lab

Understanding the cellular events that influence the aggressiveness of tumors and patient clinical outcome

Research Description

The major focus of the Horiuchi lab, established on April 1, 2015, is on the mechanisms of tumor maintenance and progression in breast cancer and to identify novel therapeutic targets and treatment strategies. To achieve these goals, we utilize a collection of human breast cancer cell lines, preclinical animal models and high-throughput screening approaches along with state-of-the-art bioinformatics through collaboration with experts in the field.

We are currently focused on the following areas:

  1. Mechanisms of tumor maintenance and progression medicated by proto-oncogenes (i.e., MYC transcription factor, PIM family of serine/threonine kinases, etc.), their activators and effectors and the tumor microenvironment.
  2. Biology and therapeutic targetability of novel molecular factors that determine patient clinical outcome.

For lab information and more, see Dr. Horiuchi’s faculty profile and lab website.

Publications

See Dr. Horiuchi's publications on PubMed.

Contact

Contact Dr. Horiuchi at 312-503-4085 or the lab at 312-503-4349.

Lab Staff

Postdoctoral Fellow

Daphne Brisard, Ratika Kunder, Lindsey Marsh, Markella Zannikou

 Hiroaki Kiyokawa Lab

Investigating the roles of cell cycle-regulatory proteins in differentiation, senescence and tumorigenesis and the cell cycle control in endocrine and reproductive organs

Research Description

We are interested in the basic mechanisms of cell cycle control, cellular senescence/immortalization and malignant transformation, with a focus on protein regulation by ubiquitination. We previously demonstrated that cell cycle regulators such as p27Kip1, CDK4 and CDC25A play highly tissue-specific roles in development and oncogenesis. Ubiquitination, the covalent modification of substrate proteins with the small 76-residue protein ubiquitin, exerts diverse regulation of the fate of substrates, including the cell cycle regulators, e.g, promoting proteolysis, altering subcellular localization and modulating enzymatic activities. Our current research is aimed at revealing novel functions of ubiquitination enzymes and their substrates in development and cancer, which is expected to identify new therapeutic targets against human diseases. The laboratory uses a combination of protein engineering, proteomics, bioinformatics, cell biological techniques such as time-lapse microscopy and 3-D culture and genetically engineered mouse models. Keywords: cell cycle, ubiquitin, ubiquitination, cancer initiation, cancer progression, knockout mice, transgenic mice, breast cancer, cyclin, diabetes, pituitary, development.

Recent Findings

  • There is a unique regulation of cell cycle progression in neuroendocrine tissues such as pancreatic islets and pituitary glands of CDK4-null mice; we have shown that in this particular type of cell cycle, Cdk4 plays an indispensable and rate-limiting role
  • CDC25A phosphatase, which activates CDK2 and CDK1, is an oncogene that plays a rate-limiting role in initiation and progression of various tumors, including breast cancer

Current Projects

We are currently investigating roles of the cell cycle machinery in differentiation, tumorigenesis and apoptosis, by combinations of mouse models and molecular analyses.

For lab information and more, see Dr. Kiyokawa’s faculty profile.

Publications

See Dr. Kiyokawa's publications on PubMed.

Contact

Contact Dr. Kiyokawa  at 312-503-0699.

Lab Staff

Postdoctoral Fellow

Xianpeng Liu

 Huiping Liu Lab

Understanding and targeting cancer stem cells and exosomes in metastasis using cutting-edge technology and novel therapeutics

Liu Lab photo

Research Description

The Liu lab studies the molecular and cellular mechanisms underlying cancer stem cells (CSCs) and metastasis through four ongoing interactive basic and translational research projects: (1) to understand CSCs, circulating tumor cells (CTCs) and their interactions with immune cells in metastasis; (2) to dissect the role of secreted and circulating exosomes in CSC functions; (3) to target CSCs with novel therapeutics, exosomes and nanoparticles in combination with immunotherapy; (4) to develop CTC and circulating exosome-based biomarkers for cancer diagnosis, therapy response and predictive prognosis.

Recent Findings

  1. CSCs seed metastases of breast cancer.
  2. A rapid, automated surface protein profiling of single circulating exosomes in human blood. (PMID: 27819324)
  3. Micro-206 inhibits stemness and metastasis of breast cancer by targeting MKL1/IL11 pathway. (PMID: 27435395)
  4. Differentiation and loss of malignant character of spontaneous pulmonary metastases in patient-derived breast cancer models. (PMID: 25339353)
  5. MicroRNA-30c inhibits human breast tumor chemotherapy resistance by regulating TWF1 and IL-11.( PMID: 23340433)

Current Projects

  1. Identify how CSCs crosstalk between themselves and interplay with immune cells in circulation thus developing innovative anti-CSC targeting therapeutics.
  2. Single cell RNA sequencing of CSCs and metastatic tumors.
  3. Dissect the role of exosomes in CSC functions and regulation of exosome functions by CSCs.
  4. Develop CSC-targeting novel microRNA therapeutics and exosome delivery tools.
  5. Discover CTC and circulating exosome-based clinical biomarkers for cancer diagnosis, treatment monitoring and prognosis.

For lab information and more, see Dr. Liu's faculty profile and lab website.

Publications

See Dr. Liu's publications on PubMed.

Contact

Contact Dr. Liu at 312-503-5248.

Lab Staff

Research Faculty

Golam Kibria, Xia Liu 

Postdoctoral Fellows

Nurmaa Dashzeveg, Andrew Hoffmann

Lab Managers

Wenjing (Kim) Chen, Dhwani Patel 

Graduate Students

Erika K. RamosRokana Taftaf

Visiting Scholars

Valery Adorno-Cruz, Hengliang Shi

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