Pilot Project Award Research

The University of Kansas Cancer Center recenlty announced the winnder of the KUCC Pilot Project awards for Spring 2017. The awards were granted to support research. We spoke to our winners and asked them to tell us about their work.

• Targeting IFITM1 in Inflammatory Breast Cancer using Phenotypic Drug Repurposing Screen
• Elucidating the Role of DCLK in Head and Neck Cancer
• Involvement of Mitochondria in Intestinal Epithelial Radio-sensitivity
• Role of O-GlcNAcylation of Ewing Sarcoma Proteins in Chromosomal Instability
• Neurochemical Mechanisms of Chemobrain

Targeting IFITM1 in Inflammatory Breast Cancer (IBC) using Phenotypic Drug Repurposing Screen

Joan Lewis-Wambi, PhD, Cancer Biology

Please explain your research.
Part of my research focuses on understanding the underlying mechanism by which breast cancer cells and breast tumors develop resistance to aromatase inhibitors (AIs) which are the standard drugs used to treat hormone-receptor positive breast cancer. Additionally, my lab also studies triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC) , two aggressive and lethal subtypes of breast cancer that are difficult to diagnose and treat. TNBC and IBC disproportionately affect African American women compared to other ethnic groups.

My laboratory has also recently identified a novel marker called interferon induced transmembrane protein 1 (IFITM1). IFITM1 appears to be highly expressed in TNBC tumors and TNBC cell lines derived from African American patients but not  from Caucasian patients. This overexpression enhances the aggressive phenotype of TNBC breast cancer cells in culture. One of my research goals is to better understand the role of interferon alpha signaling in the pathogenesis of TNBC in African American patients and to conduct translational research to assess whether targeting IFITM1 has therapeutic benefits.

Why are you interested in this research area and what do you hope to learn?
Breast cancer has touched the lives of several family members and friends over the years. I am interested in studying how patients develop resistance to current endocrine therapies. Resistance to these therapies is a major clinical problem for 40-50 percent of patients, negatively impacting their quality of life and overall survival.

Through my research I hope to gain a better understanding of why breast cancer patients develop resistance to endocrine therapies and to identify novel therapeutics to treat the resistant tumors and prolong survival.

Elucidating the Role of DCLK in Head and Neck Cancer

Sufi Thomas, PhD, Otolarngology
Please explain your research.
Conventional cancer therapy targets rapidly dividing cells within tumors. However, a small percent of the tumor cells escape therapy because they are not dividing. These cells also known as cancer stem cells, are responsible for tumor recurrence. We have identified a molecule that plays an important role in head and neck cancer stem cells and is a putative target for therapy.

Why are you interested in this research area and what do you hope to learn?
Tumor recurrence contributes to low 5-year survival in head and neck cancer patients. Developing a therapeutic approach that reduces tumor recurrence rates is a critical need.

Through this work we will establish the role of DCLK1 in head and neck cancer stem cells. We will also test the antitumor efficacy of targeting DCLK1.

 

Involvement of mitochondria in intestinal epithelial radio-sensitivity

Subhrajit Saha, PhD, Radiation Oncology

Please explain your research. 
Radiation induced intestinal injury is the major limiting factor for definitive radiotherapy of abdominal malignancies, such as, gastric, pancreatic and colorectal cancer. The intestinal epithelium is highly radio-sensitive. However, fundamental mechanisms influencing radio-sensitivity still remain unclear.

Our previous studies suggested that mitochondrial content is a determining factor for radio-sensitivity. My laboratory is currently evaluating the role mitochondria in radiation response of intestinal stem cells.

Why are you interested in this research area and what do you hope to learn?

Radiation therapy has not yet entered the era of precision medicine. Yet the differences in patients’ individual radio-sensitivity significantly impacts treatment outcome and post therapy life quality. The determination of radio-sensitivity in patients is crucial to deliver tolerable dose.

This study will contribute significantly in understanding of intestinal epithelial response to radiation. I hope that at the end of this study we will identify the intrinsic factor or factors determining the variability in radio-sensitivity among patients.

Role of O-GlcNAcylation of Ewing sarcoma proteins in chromosomal instability

Mizuki Azuma, PhD, Molecular Biosciences

Please explain your research.
Ewing sarcoma is the second most common form of bone cancer in children.  In collaboration with Dr. Chad Slawson, University of Kansas Medical Center​, we aim to identify the molecular mechanism for Ewing sarcoma.  This study may have an impact on public health because it could lead to the discovery of diagnostic markers of cancer and drugs for patient therapy.

 

Neurochemical Mechanisms of Chemobrain

Michael Johnson, PhD, Chemistry and Neurosciene
Please explain your research.
We are interested in understanding the underlying chemical mechanisms of chemobrain, a condition characterized by cognitive impairment.

Currently, we are evaluating the effects of chemotherapeutic agents on cognitive impairment and neurochemical alterations, such as the ability of the neurons to release neurotransmitters and the production of hydrogen peroxide, a reactive oxygen species, on sub-second timescales.

Why are you interested in this research area and what do you hope to learn?
We are interested in this particular area because roughly a third of the 14 million chemotherapy patients will experience chemobrain. Also, little is known about the underlying mechanisms and there is currently no effective treatment.

This is really just the beginning for us. We hope to learn how alterations in neurotransmitter release patterns in behaving rats, gene regulation patterns, and morphological changes to neurons contribute to different components of cognitive impairment. Understanding these factors will hopefully facilitate the development of therapies.