Dr. Neman’s current research investigates the biology and tumor microenvironment of medulloblastoma (the most lethal pediatric brain tumor) and breast to brain metastatic tumors. His expertise and strengths in stem cell biology and neuroscience have allowed him to develop novel molecular, cellular, and systems approach to study the interaction between the brain and cancer cells –a bidirectional interplay poorly understood. Furthermore, Dr. Neman’s overall research goals are to 1) innovatively enhance and exploit the tumor-brain microenvironment, 2) identify the cellular roots of treatment failure and 3) test agents to selectively attack the resistant cells, in order to better treat patients with brain tumors.
Research on Breast to Brain Metastasis
While most people are aware of primary breast cancer, many forget that it is the metastasis that is the patient’s ultimate malice. Breast cancer metastasizes to the brain in approximately 30-40% of patients with either triple negative or Her2+ subtype. 90% of patients with these breast cancer subtypes will die of metastasis to the brain. While targeted therapies have improved management of the disease outside of the brain, poor bioavailability to the brain increases its potential as a sanctuary site for metastatic disease.
Metastasis is the result of successful interplay between tumor cells and newly encountered microenvironments. After crossing the brain’s protective gateway (blood-brain-barrier), disseminated breast cancer cells arrive in a dynamic cellular and molecular landscape that presents unique selection pressures. Much of what we know about the brain’s microenvironment comes from the field of neurobiology. Thus, as neuroscientists, our approach is to study breast cancer and its ultimate metastasis to the brain from the perspective of the brain.
Research on Pediatric Medulloblastomas:
Brain tumors are the most common cause of childhood oncological death. Furthermore, medulloblastomas (MBLs), originating in the cerebellum, are most common malignant pediatric brain tumors. MBL therapy includes surgical resection, aggressive chemotherapy, and usually also irradiation, but high risk patients continue to have poor survival. Moreover, survivors are often left with significant neurological, intellectual, and physical disabilities.
Recent evidence suggests that MBLs comprises at least 4 molecularly distinct subgroups (WNT, SHH, Group 3 and Group 4) which differ clinically and molecularly. It is currently thought that most MBL arise from cerebellar granule neuron precursor cells (cGNPs), which reside in the external granular layer (EGL) that transiently lines the outer surface of the fetal/perinatal cerebellum. The transcription factors, MYC and MYCN, are overexpressed in many MBLs. MBL show increased levels of the GABAergic receptor with dependence on this receptor for growth. However, the role of the MBL adaptation to its cerebellar microenvironment is only scantly understood. Therefore, our goal is to elucidate the tumor microenvironment in these pediatric brain tumors and develop an effective treatment for childhood with medulloblastomas.
Role of the Neural Niche in Brain Metastatic Cancer. Cancer Res. 2014 Aug 1; 74(15):4011-4015. View in: PubMed
Therapeutic disruption of the blood brain barrier in metastasis. Neurosurgery. 2014 Apr; 74(4):N11-2. View in: PubMed
Human breast cancer metastases to the brain display GABAergic properties in the neural niche. Proc Natl Acad Sci U S A. 2014 Jan 21; 111(3):984-9. View in: PubMed
Co-evolution of breast-to-brain metastasis and neural progenitor cells. Clin Exp Metastasis. 2013 Aug; 30(6):753-68. View in: PubMed
Lineage mapping and characterization of the native progenitor population in cellular allograft. Spine J. 2013 Feb; 13(2):162-74. View in: PubMed
Altered expression of polycomb group genes in glioblastoma multiforme. PLoS One. 2013; 8(11):e80970. View in: PubMed
A method for deriving homogenous population of oligodendrocytes from mouse embryonic stem cells. Dev Neurobiol. 2012 Jun; 72(6):777-88. View in: PubMed
Genetic mutations and tissue type lead to heterogeneous metabolic profiles in tumors. Neurosurgery. 2012 Jun; 70(6):N20-1. View in: PubMed
Stem cell-mediated osteogenesis: therapeutic potential for bone tissue engineering. Biologics. 2012; 6:47-57. View in: PubMed
Clinical efficacy of stem cell mediated osteogenesis and bioceramics for bone tissue engineering. Adv Exp Med Biol. 2012; 760:174-87. View in: PubMed
Cytotoxic T lymphocyte trafficking and survival in an augmented fibrin matrix carrier. PLoS One. 2012; 7(4):e34652. View in: PubMed
Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy? Neuroimage. Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy? Neuroimage. 2011 Jan; 54 Suppl 1:S106-24. View in: PubMed
Emerging role of brain metastases in the prognosis of breast cancer patients. Breast Cancer (Dove Med Press). 2011; 3:79-91. View in: PubMed
Classification of genomic changes in breast cancer brain metastasis. Neurosurgery. 2010 Aug; 67(2):N18-9. View in: PubMed
Translational emphasis: hypoxia and vasculogenesis in glioma recurrence. Neurosurgery. 2010 Jun; 66(6):N20-1. View in: PubMed
Decreasing glioma recurrence through adjuvant cancer stem cell inhibition. Biologics. 2010; 4:157-62. View in: PubMed