Hi! My name is Nicole Horan and I am a rising senior majoring in Neuroscience and Molecular Biology with a minor in Chemistry. The main reason I got into neuroscience stemmed from my frustration of the answer “We don’t know that yet”. Frequently, my questions about the brain or the biology behind behavior were met with this answer. It seemed to me that we knew more about outer space or the deep oceans than we did about the lump of tissue sitting within our cranium, especially when it came to things that could go wrong . My passion in the field is driven by my desire to uncover the unknown to ultimately help people suffering from debilitating neurological diseases.
My hometown is on the eastern side of PA in Kennett Square, and I have an energetic yet demanding Shetland Sheepdog named Barney. I grew up playing softball and volleyball, as well as being in the marching band in high school. I have continued on my love for music here in college, as I am a section leader for the marching band this year! I have been involved with the band throughout my college experience, and I really have enjoyed every second of it. I am thrilled to be a part of the Brackenridge community this summer and look forward to the opportunities and knowledge it will bring!
My Research: The Biology Behind Oral Cancer Pain
My project focuses on the biology of pain associated with oral squamous cell carcinoma. I will be working in UPMC Hillman Cancer Center under Dr. Nicole Scheff, Megan Atherton, and Dr. Lisa McIlvried.
Patients who develop Head and Neck Squamous Cell Carcinoma often experience more severe pain and stress in response to normally non-painful stimuli (ex. eating, talking, swallowing, drinking) than other cancers1 . Obviously, experiencing pain during these daily activities has a severe negative impact on these patients’ quality of life. There are two different divisions of the nervous system to consider during this study: sensory neurons that bring information to the brain and effector neurons that send signals out of the brain.
The sensory neurons to consider in this project are called nociceptors, which are crucial to perceiving pain in response to stimuli. Under normal circumstances, these neurons should not be activated by simple actions like chewing or talking, yet cancer patients experience severe pain with these activities. Our aim is to characterize and understand why that sensitized pain develops in the first place.
The effector neurons that are important in my research are part of the sympathetic nervous system. This system is in charge of your fight or flight responses during stress; by using the communicator molecule ( neurotransmitter) norepinephrine, it is able to send signals to its target organs to evoke the proper responses. This could be your heart rate increasing, your digestion stopping, or your breathing getting faster in attempts to prepare you for whatever stressor your body is reacting to. However, cancer patients suffer from chronic stress that can influence their cancer2. These sympathetic nerves that innervate the tumor can cause release of norepinephrine in the surrounding area. Previous studies have shown that the tumor cells respond to this norepinephrine with increased proliferation and release of signaling molecules into the area which can affect other cells3. This has an important clinical aspect, as patients with more sympathetic innervation to their tumor suffer from a worse prognosis4.
Oral cancer is not an isolated process, vasculature and nerves invade into the tumor and result in an interplay of different systems. We use mice models to replicate this cancer as well as human tissue donated at the cancer center to study what is going on in the brain and in the cancer microenvironment within the tumor.
The Significance Behind the Science
This research is very important because it provides an avenue for further potential of treatment. Existing painkillers do not effectively treat the pain, and opioids that are able to treat the pain become less effective as tolerance develops. Additionally, drugs that have previously been designed in attempts to reduce pain have shown to repress the immune system and hinder the body’s ability to naturally fight the cancer5. If we want to ultimately develop a long-term pharmacological treatment for these patients suffering from oral cancer related pain, we first must understand the biological processes behind it.
My Professional Goals and the Brackenridge Fellowship
My current professional goals are to eventually end up in a research and development team in a pharmacology company to develop medications for neurobiological diseases. I believe that the Brackenridge will help me pursue those goals in more than one way. First, it enables me to do summer research and learn about presenting to different audiences. In order to make research accessible, a huge step is being able to communicate to people outside the field in a comprehensible manner. Secondly, I’m excited to learn about different areas of research outside my own field. Great solutions to problems come from an interdisciplinary approach, and exposure to different research areas allows me to learn more than I would have in classes for my major.
1.) Chen AM, Jennelle RL, Grady V, Tovar A, Bowen K, Simonin P, Tracy J, McCrudden D, Stella JR, Vijayakumar S. Prospective study of psychosocial distress among patients undergoing radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2009 Jan 1;73(1):187-93. doi: 10.1016/j.ijrobp.2008.04.010. Epub 2008 May 29. PMID: 18513884.
2.)Lamkin DM, Sloan EK, Patel AJ, Chiang BS, Pimentel MA, Ma JC, Arevalo JM, Morizono K, Cole SW. Chronic stress enhances progression of acute lymphoblastic leukemia via β-adrenergic signaling. Brain Behav Immun. 2012 May;26(4):635-41. doi: 10.1016/j.bbi.2012.01.013. Epub 2012 Jan 25. PMID: 22306453; PMCID: PMC3322262.
3.)Bernabé DG, Tamae AC, Biasoli ÉR, Oliveira SH. Stress hormones increase cell proliferation and regulates interleukin-6 secretion in human oral squamous cell carcinoma cells. Brain Behav Immun. 2011 Mar;25(3):574-83. doi: 10.1016/j.bbi.2010.12.012. Epub 2010 Dec 25. PMID: 21187140.
4.)Amit, M., Takahashi, H., Dragomir, M.P. et al. Loss of p53 drives neuron reprogramming in head and neck cancer. Nature 578, 449–454 (2020). https://doi.org/10.1038/s41586-020-1996-3
5.) Jensen, A.W.P.; Carnaz Simões, A.M.; thor Straten, P.; Holmen Olofsson, G. Adrenergic Signaling in Immunotherapy of Cancer: Friend or Foe? Cancers 2021, 13, 394. https://doi.org/10.3390/cancers13030394