Matthew Miller, PhD
Assistant Professor, Department of Biochemistry and Biomedical Sciences
Associate Chair and Assistant Dean, Biochemistry Graduate Program
The Miller Laboratory is focused on understanding the intimate relationship between viral pathogens and their hosts. Upon infection, both the innate and the adaptive branches of the immune system are mobilized with the aim of protecting the host from virus-mediated pathologies. However, improper regulation of anti-viral immune responses can themselves lead to disease. In addition, viruses have – and continue to – evolve elegant strategies through which to avoid host-mediated immune recognition. Thus, understanding the qualities of immune responses which are effective in protecting the host, as well as those qualities that may cause harm, is essential to informing the development of novel vaccines and therapeutics. The Miller Laboratory is therefore interested in issues concerning both of the (1) innate and (2) adaptive branches of the antiviral response:
- The type I interferon system represents the primary innate response pathway initiated upon viral infection. Type I interferons elicit potent cell-intrinsic and cell-extrinsic mechanisms to combat infection. However, when improperly regulated, these responses can lead to devastating immunopathologies. Polymorphisms in genes responsible for regulation of the type I interferon response can therefore have a profound effect on the outcome of viral infections. Our group is interested in understanding how host genetics contribute to the pathological outcome of viral infections. Identification and characterization of these factors will be used to inform more personalized approaches to the treatment of infectious diseases.
- Influenza A virus (IAV) presents a particularly formidable challenge to control by the humoral arm of the adaptive immune system. The virus has a segmented, RNA genome which is capable of both rapid mutation (contributing to “antigenic drift”), and re-assortment (which causes “antigenic shift”). These properties allow the virus to cause seasonal epidemics and periodic pandemics, respectively. Current-generation IAV vaccines must be administered seasonally, and provide optimal protection against only a very limited number of IAV strains. However, a new class of antibodies has recently been discovered which is capable of providing much more broad protection across multiple IAV subtypes. Our group is focused on understanding the immunobiology of these antibodies, how they are elicited, and how they may be useful for the generation of “universal” influenza virus vaccines and therapeutics.