Idea Awardees

Current Awardees

headshot of Dr. Meenal Mehrotra 

Meenal Mehrotra, M.D., Ph.D.

Assistant Professor, Department of Surgery

Project: CD36-Sphingolipid Axis in Regulating Osteosarcoma Progression

Bone is a complex connective structure made up of osteoblasts (which lay down new bone) and osteoclasts (which break down bone matrix). Osteosarcoma, the most common primary bone malignancy, accounts for 2.4% of cancers in children and young adults but 8.9% of cancer deaths in this group. Despite thorough surgery and radio/chemotherapy, overall survival rates have plateaued at 60%, with 25–30% of patients not responding. Thus, novel therapies are needed.

This project looks at the tumor microenvironment (where the tumor grows). According to our research, non-malignant osteoblasts can increase the spread of osteosarcoma. Our theory is that non-malignant osteoblasts produce a sphingolipid that is released into the microenvironment and, once there, acts on osteosarcoma cells and increases the cancer’s growth and spread. We will block connections between the production and release of this sphingolipid and measure how that affects the osteosarcoma progression. Since this technique has never been investigated, we hope it will fill gaps in therapy, quality of life, and survivability and enhance osteosarcoma research.

 

headshot of Dr. John Wrangle 

John Wrangle, M.D. 

Associate Professor, Department of Medicine

Co-Investigators: Martin Kang, Ph.D., Aguirre De Cubas, Ph.D.

Project: Leveraging Lineage Addiction: Nuclear Delivery of Therapeutic DNA Constructs Responsive to Oncogenic Transcription Factor Over-Expression

We are developing gene therapy for cancer. Using viruses that naturally infect human cells, we are developing new “software” programs that inside the nucleus of a cancer cell will force the cancer to produce therapies that kill the cancer itself. We are starting with developing an anti-cancer software program for lung cancer, but if successful the therapy approach will be applied to almost any human cancer.

Previous Awardees

Paramita Chakraborty

Paramita Chakraborty, Ph.D.

Instructor, Surgery

Project: Carbon-Monoxide Mediated Transient ER Stress and Autophagy to Rescue Anti-Tumor T-Cell Exhaustion

This project will test whether moderately stressing the endoplasmic reticulum — an organelle in cells that is involved in protein quality control — could reinvigorate exhausted anti-tumor T-cells. T-cells typically activate in response to a new infection. But when the foreign agent persists, such as with HIV, hepatitis C or cancer, the T-cells can become exhausted, no longer performing at their prime. This exhaustion is a key factor in limiting the long-term success of adoptive T-cell therapy, in which a patient’s T-cells are removed, modified in the lab to better fight the cancer and then returned to the patient.

There is a delicate balance between just enough and too much stress to the endoplasmic reticulum (ER). Unending stress leads to mitochondrial collapse, but moderate stress can actually improve mitochondrial function, including in the mitochondria of T-cells. Strategies to boost anti-tumor T-cell function by targeting ER-mitochondria crosstalk have yet to be exploited. The therapeutic effects of low-dose CO led to numerous ongoing clinical trials in various disease models. However, low-dose CO has not been tested yet to improve T-cell anti-tumor potential.

 

Subramanya Pandruvada

Subramanya Pandruvada, Ph.D.

Assistant Professor, Oral Health Sciences

Project: Augmenting Immune Response in Head and Neck Cancers

This project is testing whether the standard vaccine components could jumpstart the body’s immune response to head and neck cancers. Half of oral cancers will return. And while immunotherapy has shown some promise, particularly for patients who are positive for human papillomavirus (HPV), only about 20% of patients respond to the checkpoint inhibitors that are used in immunotherapy.

Tumors are classified as “hot” or “cold” based on whether the body’s immune cells, such as T-cells, are attempting to fight them. Hot tumors are already in a battle with the body’s immune system. Cold tumors suppress the immune system, so T-cells haven’t mounted a response. In addition, people with “hot” tumors tend to respond better to these checkpoint inhibitor treatments. Developing methods to switch cancers from the ‘cold’ to ‘hot’ state is therefore vital to achieving a therapeutic effect.

Vaccines have been used before to “wake up” the immune system. The tuberculosis vaccine is FDA-approved to treat bladder cancer, and recent research has suggested that the flu vaccine could reduce tumor growth in lung cancer. Pandruvada hypothesizes that activating non-tumor-specific immune response would surge immune infiltrates locally and corroborate tumor clearance in HPV-negative oral cancer patients. This potential therapy is inexpensive and widely available, but it would also eliminate the need to develop multiple drugs against individual targets. Successful validation of the hypothesis will have important implications for repurposing several FDA-approved adjuvants in priming patients to respond to existing immunotherapies.

 

joseph delaney

Joe Delaney, Ph.D.

Assistant Professor, Biochemistry and Molecular Biology

Project: Combination of Autophagy Selective Therapeutics (COAST) in Advanced Solid Tumors or Relapsed Prostate Cancer, a Phase I Clinical Trial

Our project expands on the “maximally tolerated drug” (MTD) concept of phase I human safety trials to determine the “maximally tolerated mixture” (MTM) of a candidate drug treatment in a human cancer trial. Cancer is a disease characterized by high mutation rates which eventually leads to drug resistance. Our hypothesis is that using multiple drugs targeting the same vulnerability will better prevent cancer from developing resistance. Many cancer drugs are toxic to normal cells. The drugs in this study were selected from those with known favorable safety profiles from years of human trials and use in general medicine. Each drug disrupts a different part of the autophagy pathway, a molecular recycling pathway known to be a vulnerability of cancer cells. Because these drugs are widely used, dosages for each drug are already known.

An initial cohort of patients will be given three autophagy drugs, each of which are safe enough to be prescribed to pregnant patients in non-cancer settings. As the trial determines that these three drugs are safe in the first group of patients, the next group will be enrolled to test an addition drug. This process continues until five autophagy drugs have been tested for safety. This phase I human trial will determine the MTM of autophagy drugs in a cancer setting in patients exhibiting advanced solid tumors. If successful, the MTM may be used in future human trials to determine if the drugs are effective in slowing cancer growth.

David Turner

David Turner, Ph.D.

Associate Professor, Pathology and Laboratory Medicine

Project: Therapeutic Potential of Targeting AGE-RAGE Signaling in Prostate Cancer

As our bodies use the sugars that we consume for energy, they generate waste products called metabolites. One such group of metabolites are known as advanced glycation end products, or AGEs for short. AGEs are highly reactive chemicals that build up in our bodies as we grow older and cause damage to our tissues and organs. Accumulation of AGEs in the body increases the occurrence of inflammation and the generation of harmful chemicals known as reaction oxygen species, both of which can cause cancer and allow it to grow more aggressively.

Our studies have shown that regular consumption of the AGEs contained in our foods can produce an environment within tissues that can help a cancer to grow at a faster rate. The funds from the Hollings Cancer Center Idea Award will allow us to develop novel experimental models to assess the therapeutic potential of reducing AGE levels for the treatment of aggressive prostate cancer. The validation of these models will allow the development of large federally funded grant applications to continue this research.

 

joseph delaney

Joe Delaney, Ph.D.

Assistant Professor, Biochemistry and Molecular Biology

Project: Mechanisms of Autophagy Drug Action and Cancer Resistance

Our lab has discovered an unlikely pair of drugs which work together to kill ovarian cancer cells. One drug now in the public spotlight, (hydroxy-)chloroquine, was originally designed to prevent malaria. Chloroquine happens to kill ovarian cancer cells by disrupting a recycling system of those cells. The other drug in the pair is an anti-HIV medication, nelfinavir mesylate, which surprisingly kills ovarian cancer by disrupting the recycling system but also by increasing the amount of cellular debris which needs to be recycled.

Our lab previously found that ovarian cancer is uniquely vulnerable to these drugs which disrupt the recycling process because ~12 genes which enable recycling are suppressed in the average tumor. While we know both drugs impact this recycling process, called autophagy, the mechanism for how these drugs impact autophagy on a molecular level remains unclear. This work is designed to approach this question in an unbiased fashion. We will use whole-genome approaches to monitoring cells which evolve in response to each drug.

 

tracy smith

Tracy Smith, Ph.D.

Assistant Professor, Psychiatry and Behavioral Sciences

Project: Comparison of Leading E-Cigarette Product Types on Relative Reinforcement Value and Tobacco Use Patterns Among Current Smokers

Electronic cigarettes (e-cigarettes) have surged in popularity in recent years, and while e-cigarettes are not harmless, they are likely less harmful than traditional cigarettes. The purpose of this project is to understand how two types of e-cigarettes, customizable tanks and pods, change the appeal and use of cigarettes among current smokers who try e-cigarettes for the first time.

In this project, 75 current smokers will receive either a placebo e-cigarette (control group), a customizable tank e-cigarette, or a pod e-cigarette. Participants will try their assigned e-cigarette and complete a variety of questionnaires about it. Participants will then take their assigned e-cigarette home to use as much or as little as they wish for a three-week period. At the end of the study, the researchers will compare how the two types of nicotine-containing e-cigarettes were used by participants and their impact on smoking behavior.

 

wenjian gan

Wenjian Gan, Ph.D.

Assistant Professor, Biochemistry and Molecular Biology

Project: Functional Analysis of SPOP in DNA Damage Response for Prostate Cancer Therapy

The major focus of Dr. Gan’s laboratory is to investigate how aberrant cell signaling pathways contribute to genomic instability and cancer progression. He is particularly interested in studying the regulatory mechanisms and physiological functions of E3 ubiquitin ligases in tumorigenesis. Specifically, his group will identify the upstream pathway regulating the activity of E3 ubiquitin ligase SPOP, and investigate the role of SPOP in genomic stability by characterizing its downstream targets in prostate cancer. These studies will significantly expand our knowledge on the tumor suppressor function of SPOP, and also provide rationale for combating prostate cancer based on SPOP genetic status.

 

erin mcclure

Erin McClure, Ph.D.

Assistant Professor, Psychiatry and Behavioral Sciences

Project: Mobile, Remote, and Individual-focused: Comparing Breath Carbon Monoxide Readings and Abstinence in Next Generation Monitors

 

viswanathan palanisamy

Viswanathan Palanisamy, Ph.D.

Associate Professor, Biochemistry and Molecular Biology

Project: Post-transcriptional Regulation of Oral Prenoplasia Progression and Regression