Education:
- PhD, University of New South Wales (Australia), 1971
Clinical/Research Interests:
Molecular studies of influenza virus.
Influenza occurs every winter, usually peaking in January in the northern hemisphere. Approximately 20,000 deaths in the US per year are attributed to influenza, many among elderly patients who have medical conditions that increase the likelihood of complications from influenza. Influenza is a significant disease in all age groups; an acute febrile illness with myalgia, headache, fever and cough. A rule-of-thumb for deciding if you have influenza rather than another respiratory virus is that if you really can't get out of bed, it's probably flu. The acute stage lasts about 3 days, but cough and malaise may last for some weeks. Influenza viruses currently circulating in the human population are classified serologically as type A (H1N1, H3N2) and type B. "H" and "N" refer to the viral surface glycoproteins hemagglutinin (HA) and neuraminidase (NA), and subtypes (e.g. 1, 3) do not cross-react in antibody tests.
Influenza vaccines are safe although somewhat variable in effect, depending on the age and immunocompetence of the vaccinee as well as the similarity of each vaccine strain to the circulating viruses. Influenza viruses undergo progressive antigenic drift; an accumulation of mutations that alter antigenic properties. Occasionally there is an antigenic shift, introducing new antigens into human influenza viruses from bird or animal viruses. Vaccine manufacture is therefore complicated by the need to update the components every year in response to mutations that alter antigenic reactivity.
Our research has had two branches, one to find ways of designing better vaccines, and the second to investigate how the virus gains entry into cells and how infection might be blocked by antiviral drugs.
Recent research highlights:
Demonstration that increase in antibodies after vaccination is inversely proportional to pre-existing antibody levels (Feng et al., 2009)
Crystal structure of an antibody bound to NA shows that an N-linked glycan is part of the epitope (Venkatramani et al., 2006).
Human influenza viruses of the H3N2 subtype have changed binding specificity as antigenic drift mutations accumulate (Gulati et al., 2013).
The structure of a new NA inhibitor bound in the active site (Venkatramani et al., 2014)
Demonstration of immunodominance of certain antigenic sites that may allow prediction of antigenic drift (Popova et al., 2012)