Carroll Lab

Steven Carroll M.D., Ph.D.

Professor and Chair
Anatomic Pathology
Clinical Pathology
Director of the Hollings Cancer Center Biorepository and Tissue Analysis Shared Resource
Director of the Carroll A. Campbell Jr. Neuropathology Laboratory (Brain Bank)
System Chief of the Pathology and Laboratory Medicine Integrated Center of Clinical Excellence and Gordon R Hennigar Jr., M.D. Endowed Chair in Pathology

Jody Longo, Ph.D.
Assistant Professor
Department of Pathology and Laboratory Medicine

Lab Members

Research Interests

The Carroll laboratory focuses on identifying the abnormalities that promote the pathogenesis of cancer and neurodegenerative diseases and using this information to develop effective new therapies. We have a particular interest in the role that the growth factor neuregulin-1 (NRG1) and its erbB receptors play in the development of these diseases.

 Clinical Manifestations of Neurofibromatosis

Cancer Biology

Our work in cancer biology is directed towards determining how neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) develop in patients with the multi-system genetic disease neurofibromatosis type 1 (NF1) with therapeutic development being the end goal. We are pursuing a two-pronged approach to achieve this goal. In our first approach, we are using our understanding of the natural history of neurofibromas and MPNSTs to guide us to existing agents that are potentially effective against these tumors. For instance, since aberrant Ras signaling is characteristic of these tumors, we have used phosphoproteomics and other approaches to identify potential druggable targets within the pathways downstream of NF1-regulated Ras proteins as well as upstream activators of Ras in neurofibromas and MPNSTs. This latter group includes receptors for the growth factor neuregulin-1 (NRG1), which led us to create mice in which we can genetically ablate these receptors and examine the effect this has on MPNST pathogenesis. Our second, longer term approach is to identify novel therapeutic targets by comprehensively defining the genomic and epigenetic abnormalities that mediate the pathogenesis of plexiform neurofibromas and MPNSTs. To achieve this, we are using cross-species comparative oncogenomics, a method in which driver mutations are first identified in a mouse cancer model and then validated in human tumors. For these studies, we have created several genetically engineered mouse models which recapitulate the process of neurofibroma-MPNST progression seen in humans. We have performed comprehensive genomic analyses (array comparative genomic hybridization, high density SNP array analyses, whole exome sequencing and whole transcriptome sequencing) of MPNSTs from these mice, together with a reference set of human MPNST tumors and cell lines, to identify the driver mutations responsible for tumor development. We have partnered these genomic analyses with functional (genome-scale shRNA) screens to identify gene products that are essential for proliferation and survival.

Ongoing work is directed towards performing preclinical trials with mouse models to test the effectiveness of drugs that target these gene products.

Our work in neurobiology focuses on Alzheimer’s disease, frontotemporal dementias and amyotrophic lateral sclerosis (ALS). Our laboratory was the first to show that NRG1, a protein that plays an important role in synaptogenesis, and its receptors are aberrantly distributed in neuritic plaques in humans with Alzheimer’s disease and genetically engineered mouse models of Alzheimer’s disease. After globally identifying the cellular populations expressing erbB receptors in the adult rat brain with immunohistochemistry and in situ hybridization, we additionally showed that NRG1 plays an important role in shaping the dendritic and axonal trees of hippocampal neurons and that this growth factor is an important survival factor for motor neurons in the spinal cord. At present, we are constructing several new genetically engineered mouse models to assess the role that specific erbB mutations play in the pathogenesis of frontotemporal dementias and ALS and to ascertain whether NRG1 can be used to slow the development of Alzheimer’s disease and other dementias.

As with our cancer work, we partner mouse and cell culture models of neurodegenerative diseases with studies of brain tissue and other biospecimens collected from patients with dementia. These studies are facilitated by the fact that Dr. Carroll is the Director of the Carroll A. Campbell, Jr. Neuropathology Laboratory, which contains a collection of several hundred brains from patients with Alzheimer’s and related dementias that have been donated for research. In collaboration with Drs. Eric Hamlett, Brad Schulte and Judy Dubno, we are using these specimens to determine whether pathologic changes affecting the brain circuitry responsible for hearing and other senses occurs in Alzheimer’s disease and whether clinical changes in these senses can be used as a biomarker for diagnosing the early stages of Alzheimer’s disease. The Carroll A. Campbell, Jr. Neuropathology Laboratory is also a founding member of an international consortium of brain banks that collect brain tissue and other research specimens from Down syndrome patients, who almost inevitably develop Alzheimer’s disease in their forties. In collaboration with Dr. Eric Hamlett and Lotta Granholm, we have used specimens from these patients to establish that changes in the protein cargo contained in neuronally-derived exosomes can be used as a biomarker for the early stages in the development of Alzheimer’s disease.

In addition to these research areas, Dr. Carroll is the Director of the Hollings Cancer Center Biorepository and Tissue Analysis Shared Resource. In this role, Dr. Carroll participates in the Human Cooperative Tissue Network, a multi-institution network that banks and distributes tumor tissue for research to investigators across the United States and elsewhere. The Biorepository is also an active participant in an effort headed by Dr. Marvella Ford that partners MUSC with South Carolina State University; this project focuses on understanding the basis for disparate outcomes in cancer patients from diverse backgrounds.