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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.

Uncovering the Biological Mechanisms of Aggressive Breast Tumors

Dai Horiuchi, PhD, assistant professor of Pharmacology, and his team are devoted to understanding the cellular events that influence the aggressive of breast tumors and discovering new therapeutic strategies to treat those tumors.

Breast Tumors Discoveries
Pioneering Academic Drug Discovery

Pioneering Academic Drug Discovery

Daniel Martin Watterson, PhD, professor of pharmacology and John G. Searle Professor of Molecular Biology and Biochemistry, studies biological mechanisms important in how cells communicate with each other. The work is advancing basic and translational knowledge about critical biological processes and molecules that regulate physiological pathways, and how they are altered in diseases such as Alzheimer’s disease, brain injury and cancer. The goal is to develop novel drug treatments that can intervene in disease progression.

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

Malorie Blancard, Hananeh Fonoudi, Mariam Jouni, Davi Leite, Tarek Mohamed, Disheet Shah

Graduate Students

Liora Altman-Sagan, K. Ashley Fetterman, Emily Pinheiro, Marisol Tejeda, Carly Weddle

Technical Staff

Mennat Gharib

 Debabrata Chakravarti Lab

Epigenome and 3D chromatin organization dysregulations define human cancers and reproductive diseases

Research Description

Dr. Chakravarti’s research is focused on understanding epigenetic and transcriptional regulation of human tumorigenesis.  One of his research projects is focused on understanding the mechanisms that drive the development of uterine fibroids and endometriosis that affect an alarmingly high number of all women.  In another project, Dr. Chakravarti’s research team investigates molecular underpinning of contribution of transcription factors, cofactors and epigenomic and 3D genome reorganization regulation of prostate Cancer that affects a large number of men worldwide.  In a third project the laboratory determines the role of protein cofactors in regulation of cell cycle genes. Thus, our work interfaces both fundamental and translational research on diseases that affect humankind.  It is our hope that when combined with results from others, our research will contribute to the development of future therapeutics.  Dr. Chakravarti gratefully acknowledges continuous funding support from the NIH and key roles of his lab members and collaborators in the overall success of the Chakravarti Laboratory.

Dr. Chakravarti also enjoys teaching.  He has continuously taught both medical and graduate students.  He serves on numerous Ph.D thesis committees.  He has trained a large number of graduate students and postdoctoral fellows some of whom are now independent investigators at this and other institutions.

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

Publications

See Dr. Chakravarti's publications in PubMed.
Associate Editor: Endocrinology 2017-present; Editorial Board:  Molecular Endocrinology 2011- present, Mol. Cell. Biol. 2014-present
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

Contact Us

Dr. Chakravarti

312-503-1641

 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.

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 Fellows

Erica Trujillo

Technical Staff

Lauren Begg, Pranathi Vadlamani

 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

Technical Staff

Cade Brittain

Temporary Staff

Asia Owais, Maysa Shemmiyeva

 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

Yuzhi Jia, Xia Liu 

Postdoctoral Fellows

Nurmaa Dashzeveg, Lamiaa El-Shennawy, Andrew Hoffmann

Lab Managers

Wenjing (Kim) Chen, Dhwani Patel 

Graduate Students

Emma Schuster, Erika K. Ramos, David Scholten, Rokana Taftaf

Technical Staff

Madoka Kawaguchi

Visiting Scholars

Valery Adorno-Cruz

 Gabriel Rocklin Lab

We develop high-throughput methods for protein biophysics and protein design, with a focus on protein therapeutics

Research Description

Key questions include: How do protein sequence and structure determine folding stability, conformational dynamics, and resistance to aggregation/degradation-inducing stresses? Can we quantitatively predict these protein "phenotypes" from genotype (sequence) using computational modeling? How do we design protein therapeutics that optimize these phenotypes for a particular application? To answer these questions, we combine large-scale de novo computational protein design with high-throughput methods such as display selections, mass spectrometry proteomics, and next-generation sequencing, enabling us to test thousands of proteins in parallel. By combining these technologies, we seek to develop efficient "design-test-analyze" cycles, iterating our way to an improved, quantitative understanding of protein biophysics and more advanced protein therapeutics.

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

Publications

See Dr. Rocklin's publications on PubMed.

Contact

Contact Dr. Rocklin at 312-503-4892.

Lab Staff

Postdoctoral Fellows

Sugyan Dixit, Jane Thibeault, Kotaro Tsuboyama

Graduate Students

Tae-Eun Kim, Cydney Martell

Research Fellow

Radhika Dalal

Technical Staff

Robert Ludwig, Claire Phoumyvong

Visiting Scholar

Allan Ferrari

 Yong Wan Lab

Defining the molecular mechanisms of breast tumor initiation, progression, and metastasis, and identifying novel targets for therapeutic development.

 Wan_lab

Research Description

The overarching goal of Wan laboratory is to define the molecular mechanisms of breast tumor initiation, progression, and metastasis, and to identify novel targets for therapeutic development. Particularly, the laboratory seeks to address how defects in the ubiquitin-proteasome system and other posttranslational modifiers such as protein methyltransferase, poly (ADP-ribose) polymerase and glycosyltransferase would result in genomic instability, deregulated tumor immune checkpoint function, abnormal cell cycle, and aberrant signaling that predispose otherwise normal cells to become cancerous tumor cells or promote cancer progression and metastasis. The research approaches in Wan laboratory include biochemical, cell biological, genetic, protein structural analyses as well as the use of breast cancer animal models and analyses of clinical specimens.

For lab information and more, see Dr. Wan's faculty profile and visit the Wan Lab website.

Recent Findings

  • Pharmacological suppression of B7-H4 glycosylation restores antitumor immunity in immune-cold breast cancers.2020. Cancer Discovery (in press)
  • EIF3H Orchestrates Hippo Pathway-Mediated Oncogenesis via Catalytic Control of YAP Stability.  PMID: 32269044
  • A novel strategy to block mitotic progression for targeted therapy. PMID: 31669221
  • A novel small-molecule antagonizes PRMT5-mediated KLF4 methylation for targeted therapy. PMID: 31101597

Current Projects

Publications

See Dr. Wan's publications on PubMed.

Contact

Contact Dr. Wan at 312-503-2769.

Lab Staff

Research Assistant Professor:

Yueming Zhu

Postdoctoral Fellows:

Cindy Mandy Wavelet
Olena Odnokoz

Graduate students:

Jack Chi
Shelby Hophan
Valentina Medvedeva

 Zhe Ji Lab

Dissecting the regulation of gene transcription and RNA translation underlying oncogenic processes.

Research Description

Cancer happens through accumulated genetic mutations and epigenetic alternation in normal cells. With the advances of genomic technologies, we now can precisely characterize the genome-wide alternations of gene expression underlying oncogenic processes in a cost-effective and unbiased manner. My lab will use the combined experimental genomic technologies and computational modeling to examine the regulation of gene transcription and RNA translation during steps of oncogenesis. We aim at revealing novel cancer therapeutic targets and strategies for precision medicine and immunotherapy.

Current Projects

Currently, we are working on the following projects.

  • Characterizing the transcriptional regulatory circuits mediating inflammation in the cancer microenvironment.
  • Examining the genome-wide regulation of RNA translation in cancers.
  • Defining the functional roles of non-canonical translation in lncRNAs, pseudogenes and 5’UTRs in cancers.

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

Publications

See Dr. Ji's publications on PubMed.

Contact

Contact Dr. Ji at 312-503-2187.

Lab Staff

Postdoctoral Fellows

Qianru Li, Hongbin Wang, Xin Wang, Haiwang Yang, Xingyu Yang

Graduate Students

Emily Stroup, Sheng Wang