Mahua Dey Lab

We investigate primary and metastatic brain tumors in adults utilizing both patient samples and mouse models in order to understand how to better utilize immunotherapy as a treatment option. As a lab, we utilize state of the art techniques such as next generation sequencing, single cell flow cytometry, optical microscopy, as well as cellular and molecular immunology and neuroscience. Our primary goal is to translate our science from bench to bedside in the form of clinical trials that can challenge the current standards of care for brain tumors.

T-Cell Senescence

T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and the present of regulatory T cells. In comparison to activated effector T cells, T cell anergy, exhaustion, and senescence can be distinguished by their unique expression, or lack of expression, of surface receptors as well as different levels of intracellular cytokines, such as CD-28, IL-2, KLRG-1, LAG-3, PD-1. As a lab we want to understand the complex role immune cell senescence plays in the treatment of brain tumors as well as how to overcome the typical senescence seen in the aging immune system.

Radiation Induced changes in Metastatic Brain tumors

Metastasis to the brain involves four major steps: Detachment of the metastatic cell from the primary cancer, survival in systemic circulation, invasion into the brain parenchyma, and survival in the CNS microenvironment. Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs), however, recurrence of the tumor is still common. We aim to understand through genomics and bioinformatics how SRS changes the molecular profile of these tumor cells in order to better understand why the tumors recur.

Epigenetic modification of Immune Cells

Epigenetics is the study of changes in gene activity that persist following cell division but do not involve alteration of the DNA nucleotide sequence. Epigenetic mechanisms, including DNA methylation, histone post-translational modifications, and chromatin structure regulation are critical for the interactions between tumor and immune cells. Emerging evidence shows that tumors commonly hijack various epigenetic mechanisms to escape immune surveillance. As a lab we want to understand how epigenetic modifications in immune cell populations are changing the phenotype of immune cells and hampering their ability to respond to the tumor.

Tumor Vaccines

One area of therapeutics our laboratory is especially interested in is tumor vaccines. Tumor vaccines rely on a priming of a patient’s own immune system to boost its ability to recognize and attack the brain tumor. We are engaged in development of both personalized neoantigen based tumor vaccines as well as novel Fusokine based immune system boosting vaccines. We conduct this research using a combination of in vivo animal modeling as well as in silico computational modeling combined with next generation sequencing and machine learning. The goal of this tumor vaccine development is a more personalized arm of treatment that can be combined with surgery and chemo/radiotherapy to increase patient survival.

LM Project

Leptomeningeal metastasis (LM), characterized by tumor cells spread over the meninges lining the brain and spinal cord and shed into the surrounding cerebrospinal fluid (CSF), commonly occurs in advanced breast cancer. LM is rapidly fatal due to poor detection and limited therapeutic options, with a median survival of 3 to 5 months. External beam radiation therapy (EBRT) targeting the whole brain and intrathecal space of the spine (craniospinal radiation) is the primary treatment for most patients with LM. However, limited success is observed due to non-sufficient effect and severe radiotoxicities. Recent developments with targeted radionuclide therapy (TRT) demonstrate great promise in specifically delivering therapeutic radiation doses to cancer and metastases while minimizing off-target tissue toxicity. Our lab aim to apply targeted radionuclide in LM in order to enable enhanced survival and reduced neurological toxicity.

Principal Investigator

Dr. Mahua Dey, MD, is an assistant professor of neurological surgery and director of surgical neuro-oncology program at the University of Wisconsin School of Medicine and Public Health. Dr. Dey specializes in surgical management of both benign and malignant brain and spinal cord tumors, including gliomas, meningiomas, acoustic tumors, pituitary tumors, metastatic brain cancer, and other skull base tumors.

Scientist

Lei grew up in Tianjin China and received his PhD from Beihang University, Beijing China. Before joining UW-Madison, he had research experience as a research associate at the Beijing Institute of Genomics, Chinese Academy of Science. His main research interests include: epigenetics, neuroscience and tumor biology. He is currently working on 1. Deciphering the role of DNA methylation in T-cell plasticity; 2. Studying the role of senescent T-cells in GBM. Outside of research, he likes soccer, hiking and music.

Jack grew up in Fond du Lac WI and did his undergrad training at UW graduating with a B.S. in Neurobiology. He then moved to Chicago and worked for 3 years in the Ahmed lab at Northwestern in the Department of Neurosurgery. At NW he broadly aimed to understand how GBM develops resistance to Temozolomide using both molecular biological and bioinformatic techniques. During his PhD work Jack is interested in focusing on using large patient datasets to try to better understand or predict which treatments for GBM will be best suited for patients. His main research interests include: bioinformatics and data science, translational animal modeling, clinical trial design, and therapeutic resistance.When not in the lab Jack enjoys spending time with friends in and around Madison, running, golfing, and travel.

Caelan grew up in Traverse City MI. He did his undergraduate training at University of Colorado at Boulder in Molecular, Cellular, and Developmental Biology while working in the Lowry Psychoneuroimmunology Lab and for Mycobacterium Therapeutics Corporation. He focused on the immune modulating effects of non-tuberculosis mycobacterium. In Dr. Deys Lab he is focusing on patient immunopathology and how it affects therapeutic efficacy as well as peripheral sampling for patient diagnostic purposes. When not in the lab Caelan enjoys playing music, sailing and skiing

Xiaohu grew up in Beijing, P.R. China. He received his B.S. in Biology from Beijing Normal University in China and his M.S. from the University of Hawaii at Manoa. He joined the Dr. Dey lab in September 2020. Before working at the University of Wisconsin, Xiaohu has more than 20 years of working experience both in the pharmaceutical industry as well as in academia.  His research expertise includes and not limited to drug development and validation, animal model development, cell culture, and molecular assays.  His current research interests include primary brain tumor and mechanisms of metastasis associated immunotherapy. In his spare time, he enjoys fishing, tennis, and exercising.