Dr. Angela Rasmussen on 12 habits that increase your risk for cold and flu viruses

I recently spoke with MSN about habits that make folks more susceptible to cold and flu.  My Ph.D. thesis research concerned mechanisms of rhinovirus pathogenesis in an animal model of the common cold.  During my graduate career at Columbia University, I studied the common cold extensively, in cell culture, mouse models, and (unintentionally) myself (living in New York City, I was exposed to a lot of cold viruses).  So I am both personally and professionally very interested in preventing cold and flu transmission.  Check it out!

http://healthyliving.msn.com/diseases/cold-and-flu/12-habits-that-make-you-a-cold-and-flu-target#1

Dr. Angela Rasmussen talks West Nile virus transmission and prevention

I was interviewed by MedHelp about the West Nile virus (WNV) epidemic here in the United States, and ways to prevent WNV and identify early symptoms of infection.  Although WNV transmission is winding down with cooler fall weather in 2012, thanks to climate change and overall warming trends, we can expect future epidemics next summer and beyond.  Warm, wet weather that facilitates mosquito breeding can lead to serious outbreaks, and we can expect more in years to come.

Check out some information about WNV, as well as tips on prevention here: http://www.medhelp.org/general-health/articles/Get-the-Facts-on-West-Nile-Virus/507

Transplant study in the news!

The University of Washington news office released an announcement to the press about the transplant study (Rasmussen et al, Hepatology, 2012; Diamond et al, Hepatology, 2012).

I am excited to report that it was picked up and reported by Science Codex!  These studies were the result of ten years' worth of hard work by a number of dedicated and brilliant colleagues, and I'm glad that our findings are getting recognized for their contributions to the field of HCV-induced liver disease pathogenesis.

(That's me.  Photo credit: University of Washington)

I'm also excited to report that Dr. Paul Ramsey, the dean of the UW School of Medicine, named these studies' publication as a top advance in the history of UW Medicine.  

http://www.uwmedicine.org/Global/About/Pages/History.aspx  (Scroll down to July 27, 2012).

It's really nice to have hard work acknowledged, but it's infinitely more satisfying knowing that I led a study which may have some real value for HCV transplant patients.  This is what science should be all about.

Ebola outbreak in Uganda

According to the World Health Organization, the first Ebola outbreak since 2009 started in Uganda in July.

http://www.who.int/csr/don/2012_07_29/en/index.html

It began in a village, and has since spread to the capital city of Kampala.  There have been 20 cases, and 14 deaths from Ebola hemorrhagic fever.

Why should you be worried?  Not planning a trip to Uganda any time soon?  Well, we still don't know for sure that Ebola can't be efficiently transmitted via the airborne route, or even what species naturally carries Ebola in the wild.  We have no drugs to treat Ebola virus, and funding for research studying drugs or vaccines is the lowest it has been in history, with more budget cuts to come in 2013.  So, nothing to worry about...right?

Editorial in Hepatology about Rasmussen et al, 2012!!!

I'm excited to report that Hepatology published my transplant study paper and the companion paper by Diamond et al which I co-authored as the cover story of the July issue!  Additionally, the editors at  Hepatology recruited some experts in HCV systems biology (including John Paul Pezacki, who is a leading researcher in the cutting edge field of activity-based proteomics) to write an editorial commenting on the significance of these manuscripts.  The editorial reports that these are "seminal systems biology studies," and discusses the molecular signatures identified by myself and Dr. Diamond as strong candidates for developing prognostic tests that might predict which patients will develop severe liver disease following a transplant.  That in turn could shape therapeutic strategy and the course of their clinical care.

Rasmussen et al, Hepatology, 2012

The transplant study is here!  This study has been going on for nearly 10 years, and represents an unprecedented use of systems biology to study liver disease in patients infected with chronic hepatitis C virus (HCV) undergoing a liver transplant.

Angela L. Rasmussen, Nicolas Tchitchek et al.  Early transcriptional programming links progression to hepatitis C virus–induced severe liver disease in transplant patients.  Hepatology 56(1): 17-27.  July 2012.
People infected with HCV develop chronic disease in 70% of cases.  Of these patients, 30% will develop severe liver disease over the course of 10-30 years.  The only treatment for liver failure caused by HCV is a liver transplant, and HCV is the leading cause for transplants in the U.S.  Unfortunately, the new liver becomes infected with HCV upon transplantation.  Even more unfortunately, HCV causes liver disease much more rapidly after transplant, likely due to the immunosuppressive drugs that are required to prevent graft rejection.   However, we do not know what types of host responses to HCV infection can predict or lead to accelerated liver disease progression.   Therefore, we studied changes in gene expression from liver biopsies taken from HCV patients over time following transplant.  We looked at gene expression from patients who did and who did not develop severe liver disease, and most importantly, we did so before any evidence of fibrosis (scarring) was obvious in the liver tissue.  This allowed us to identify critical genes linked to severe disease before disease was ever evident, paving the way to develop a test that might predict which patients are at risk of developing severe liver disease.  If we can predict which patients might progress, we can intervene at an earlier stage using a variety of aggressive clinical strategies to halt liver disease progression before any damage is done.

We also performed a companion study by Diamond et al, which I co-authored, that identified similar proteomic signatures in a subset of these patients.

Deborah L. Diamond, Alexei L. Krasnoselsky, Kristin E. Burnum et al.  Proteome and computational analyses reveal new insights into the mechanisms of hepatitis C virus–mediated liver disease posttransplantation.  Hepatology 56(1): 28-38.  July 2012.

Rasmussen et al, J Virol, 2011

This is the first paper I published during my postdoctoral fellowship in Dr. Michael Katze’s lab at the University of Washington.

Angela L. Rasmussen et al. Systems Virology Identifies a Mitochondrial Fatty Acid Oxidation Enzyme, Dodecenoyl Coenzyme A Delta Isomerase, Required for Hepatitis C Virus Replication and Likely Pathogenesis.  Journal of Virology 85(22): 11646-11654.  November 2011.

In this manuscript, I used computational models of proteomic and metabolomic data from infected cells in culture and patient liver biopsies to identify an enzyme, DCI, that is predicted to be a key regulator of host responses to hepatitis C virus (HCV).  Using lentiviruses expressing short hairpin RNAs (shRNA) targeting DCI, I stably “knocked down” DCI expression in the Huh7 human hepatoma cell line.   HCV replication was completely blocked in DCI knockdown cells compared to wild-type or non-targeting control cells, indicating that DCI is required for productive HCV infection.

DCI is an enzyme upstream of the fatty acid beta-oxidation pathway, and blocking this pathway with a pharmocologic inhibitor produced similar inhibition of HCV, indicating that fatty acid oxidation is essential for HCV replication.  I am currently following up on these results to determine the exact mechanism underlying the requirement for DCI.  I am using the DCI knockdown line to generate metabolomics and genomics data sets, to look at global changes in cellular lipids and gene expression, coupled with more traditional techniques such as confocal microscopy and western blotting.  I hope to publish on my new findings in the next 6 months, so stay tuned to find out exactly how HCV requires fatty acid oxidation and DCI to support infection.