D I V I S I O N  O F  N E U R O P A T H O L O G Y

U n i v e r s i t y  o f  P i t t s b u r g h  S c h o o l  o f  M e d i c i n e

D e p a r t m e n t  o f  P a t h o l o g y


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Ronald Hamilton, MD

Research Interests:
Dr. Hamilton has research interests in the molecular biology of brain tumors, and Chronic Traumatic Encephalopathy.  His brain tumor research is primarily on paraffin-embedded human brain tissues.

Opportunities for Fellows:
Fellows have the opportunity to engage in immunohistochemical studies and can participate in neuro-oncology work with clinico-pathologic correlations using immunohistochemistry (proliferation rates and other molecular markers of malignancy) or correlation of loss of heterozygosity and tumor progression.

Opportunities for Graduate Students:
None at this time.

Opportunities for Undergraduates:
None at this time.

David Lacomis, MD

Research Interests:

Dr. Lacomis specializes in neuromuscular diseases and neuromuscular pathology.  His major research interests are the identification of biomarkers and treatment trials in amyotrophic lateral sclerosis (ALS) and in the pathology of inflammatory and critical illness myopathies.  He collaborates in developing an induced pluripotent stem cell program and in a serial study of high field fiber tractography, both in ALS.

Clayton Wiley, MD, PhD

Biomarkers of Neuroinflammation:

In the recent past we have collaborated with the Positron Emission Tomography (PET) Center to image macrophage activation in human and non-human primate models of neurological disease. Using a novel radioligand (PK11195) to assess activated microglia in brains of living HIV-infected human and SIV-infected primates, these studies demonstrated the feasibility, but limited sensitivity of PK11195 PET in monitoring CNS inflammation (Venneti et al., 2008; Venneti et al., 2004; Venneti et al., 2009; Wiley et al., 2009).

While performing the PET studies, we took advantage of the study’s serial time points to discover biomarkers of neuroinflammation in serum and CSF. Using unbiased proteomic analysis with SELDI-TOF mass spectrometry, we discovered a highly sensitive and reproducible biomarker of CNS inflammation, Chitinase 3-like 1 protein (CHI3L1). We and other groups have since observed expression of CHI3L1 in a broad spectrum of CNS inflammatory diseases (Alzheimer’s disease (AD), traumatic brain injury (TBI), Multiple sclerosis (MS) etc.) (Bonneh-Barkay et al., 2010).

Control of neuroinflammation:
While of great utility as a biomarker, CHI3L1 is becoming even more important as a member of a new class of proteins mechanistically involved in the control of neuroinflammation. These novel proteins modulate the interaction between inflammatory cells and CNS extracellular matrix. Using transgenic mice where the mouse homolog of CHI3L1 was deleted by homologous recombination, we have examined the role of this protein in animal models of MS (EAE) and TBI (Bonneh-Barkay et al., 2012). In both models, deletion of CHI3L1 led to worse clinical and pathological outcome. Current studies in our lab are aimed at elucidating the molecular mechanism by which CHI3L1 limits inflammation and how to mimic its action using small molecules. These studies hold the potential of developing novel therapies to decrease neuroinflammation, potentially supplementing or synergistically interacting with current anti-inflammatories.

Age related neurodegeneration:
While intuitively obvious, it warrants remembering that the single most important determinant of neurodegeneration is age. Through extensive collaborations with the Alzheimer’s Disease Research Center, we clinically document the neuropathology of AD and related diseases. The beta amyloid hypothesis of AD proposes that toxic fragments or oligomers of beta amyloid mediate neurodegeneration. We and others have explored the capacity of active immunization to eliminate beta amyloid from the aging primate brain (Kofler et al., 2012). Current studies in the lab are examining how lentiviral infection and combined anti-retroviral therapy modulate age related neurological processes and gene expression associated with neurodegeneration.

Viral encephalitis:
Collaborations with other Pittsburgh investigators have allowed us to expand our studies of the brain’s susceptibility to viral infections. Working with Drs. Ted Ross and Doug Reed, we have discovered the heightened susceptibility of the brain to aerosol transmission of common viral pathogens. Arboviruses that normally infect through insect vectors cause limited systemic disease, but when delivered through aerosol route, they rapidly cause lethal encephalitis. How the brain’s innate immune response and systemic adaptive immunity protect the CNS is a current focus of the lab. In collaboration with Dr. Ross, we have discovered that host exposure to seasonal influenza determines susceptibility to lethal avian influenza. Newly proposed studies will elucidate the role of innate and adaptive immunity in conferring this protection. Importantly from a public health perspective, this team is also researching how immunization protects or predisposes to encephalitis.

Opportunities for Fellows: Post-doctoral fellows with a solid foundation in either molecular biology or immunology are encouraged to expand their training in the study of neurological disease while at the same time creating their own experimental niche investigating the pathogenesis of neurodegeneration and encephalitis.

Opportunities for Graduate Students: Graduate student projects are directed along the lines of existing funded studies including: elucidation of immune cell trafficking to the brain, pathogenesis of viral encephalitis, alterations in gene expression during encephalitis, adaptive and innate immune control of CNS infections and in vivo monitoring of neuroinflammation.

Opportunities for Undergraduates: At any one time the laboratory sponsors 1 or 2 undergraduate students. Undergraduates begin lab work with routine experiments, and based upon performance, may be paired with fellows or graduates students to carry out more advanced studies.


Bonneh-Barkay, D., et al., 2012. Exacerbation of experimental autoimmune encephalomyelitis in the absence of breast regression protein 39/chitinase 3-like 1. Journal of neuropathology and experimental neurology. 71, 948-58.

Bonneh-Barkay, D., et al., 2010. In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases. J Neuroinflammation. 7, 34.

Kofler, J., et al., 2012. Preventive immunization of aged and juvenile non-human primates to beta-amyloid. Journal of neuroinflammation. 9, 84.

Venneti, S., et al., 2008. Longitudinal in vivo positron emission tomography imaging of infected and activated brain macrophages in a macaque model of human immunodeficiency virus encephalitis correlates with central and peripheral markers of encephalitis and areas of synaptic degeneration. Am J Pathol. 172, 1603-16.

Venneti, S., et al., 2004. PET imaging of brain macrophages using the peripheral benzodiazepine receptor in a macaque model of neuroAIDS. J Clin Invest. 113, 981-9.

Venneti, S., et al., 2009. PK11195 labels activated microglia in Alzheimer's disease and in vivo in a mouse model using PET. Neurobiol Aging. 30, 1217-26.

Wiley, C. A., et al., 2009. Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol. 66, 60-7.