Snyder Research


Name: Christopher M. Snyder
Position: Associate Professor

233 South 10th Street
Suite 730
Philadelphia, PA 19107

Contact Number(s):

Cytomegalovirus (CMV) is herpesvirus that infects most people in the world. Like all herpesviruses, CMV establishes a life-long infection that must be continuously controlled by the person's immune system. As a result, the consequences of CMV infection depend on the immmune state of the host. CMV causes significant disease  in children who were infected before birth (immune immature), and transmission to a developing fetus in utero is remarkably common (~0.1 - 0.2% of all newborns in the US) with devastating consequences including hearing loss, vision impairment and cognitive/motor deficits. CMV also causes severe illness in people who become immune compromised later in life, and it is the most common infectious complication of transplantation. Finally, CMV impacts aging and has been associated with chronic inflammation in old age and the development of cardiovascular disease, immune senescence and macular degeneration.

The primary interest of the Snyder lab is to understand the interaction of CMV with the immune system and the consequences of these interactions in different tissues over the life-span of the host. 

Research Projects

Immunity to cytomegalovirus in mucosal tissues

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Protection against CMV will depend on stopping the virus at the site of entry or preventing infection of the fetus by stopping the virus as it disseminates through the body. In pursuit of this, our lab is investigating: i) immunity at a natural site of viral infection (the nasal mucosa), ii) how protective responses can be targeted to this tissue, iii) how CMV spreads within its host and iv) how the immune system can interrupt viral transit and shedding.

MCMV-driven immune pathology in the developing and aging eye

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Vision impairment is a common outcome of congenital CMV infection. However, the mechanisms of disease are unknown and no animal models exist to begin dissecting pathophysiology or developing interventions. Our data suggest that MCMV infection of newborn BALB/c mice (a model of congenital infection) results in infection of the retina, large numbers of infiltrating hematopoietic cells, and markedly disrupted retinal development with focal distortions in the inner and outer nuclear layers. Importantly, our data suggest that the immune response to MCMV is responsible for the observed pathology and that blocking immune infiltration of the eye can prevent retinal damage. Our current goals are to identify the mechanisms of disease, in order to define novel targets for inhibition of the immune system that will prevent retinal disease without compromising systemic viral control.

The use of cytomegalovirus to modify the tumor environment

Despite substantial effort, vaccines that elicit effective anti-tumor immunity are rare. Cytomegalovirus (CMV) is a herpesvirus that causes minimal or no disease in immune competent hosts, but still stimulates the largest known T cell populations in the circulation of adults. Recent work has shown that CMV-based vaccine vectors stimulate incredibly strong immune responses. Thus, CMV-based vaccines for humans are currently in development. However, while substantial pre-clinical data demonstrates the efficacy of CMV-based vaccines for infectious diseases including HIV, very little is known about how effective CMV-based vaccines will be for tumors. We have been exploring the efficacy of CMV-based vaccines in mouse models of melanoma and squamous cell carcinoma using the natural mouse CMV (MCMV). Unexpectedly, we found that direct intratumoral infection by MCMV had a profound influence on the tumor environment and promoted T cell-mediated destruction of tumors, without the use of foreign antigens in the tumor, adoptive T cell therapy to enhance T cell numbers, or checkpoint blockers to alleviate immune suppression. Remarkably however, blocking the immune checkpoint PD-1 robustly synergized with MCMV infection to destroy well-established melanomas. This effect was largely, but not completely dependent on CD8+ T cells in the mouse. Our data suggest that MCMV alters the tumor environment through infection of tumor associated macrophages and recruitment of new macrophages into the tumor. With this system, we investigate how MCMV and its human counterpart  (HCMV) modulate macrophages and how this infection impacts the tumor environment to facilitate T cell-mediated immune destruction.