Professor
Pathology and Laboratory Medicine
University of Wisconsin-Madison
555 Science Drive
Madison, WI 53711
Ph: 608-890-0845
Fax: 608-265-8084

Dave's Calendar
Dave's CV


Happy ThanksTWiVing

Hi to anyone who is visiting this site after listening to This Week in Virology. It was great to have an opportunity to discuss our research. I’ll use Google Analytics to see if get a TWiV bump! If anyone is interested in getting more frequent updates on our work, I encourage you to follow me (@dho) on Twitter.

Here are a few links to topics we discussed on TWiV:

- Michael’s original paper on simian hemorrhagic fever viruses in red colobus monkeys [congrats to Michael, who finished his PhD in August!]
- Haddock and Dunn’s outstanding book ‘Practical Computing for Biologists
- information about the Illumina miSeq deep sequencer
- articles with my Brazilian friends describing deep sequencing of dengue, HIV [note, while looking for this URL I stumbled across an article in GenomeWeb I didn’t know existed!], and hepatitis C viruses

...and finally, my pick of the week (which didn’t make the podcast, unfortunately)...the Sonos Wireless Speaker System, which we just used to listen to TWiV in every room of our house!

It’s been a few months since the last website update, so here’s a quick summary of what we have been doing...

A lot of our time has been spent analyzing whole genome sequencing data from 20 SIV+ Mauritian cynomolgus macaques. These datasets are huge! Thanks to the outstanding best practices tutorials from the Broad Institute, we’ve begun calling and analyzing variants from these datasets. Adam Ericsen, Salendra Singh, and two rotating graduate students, Shelby Malone and Nick Florek, have done a great job exploring a possible relationship between a genomic region containing the granzyme B gene and control of SIV replication. The simple genetics of Mauritian macaques are ideal for exploring how immune genetics influence infectious disease resistance.

Our genetics team has also been working hard to understand macaque MHC diversity. Dawn Dudley described a new technique for identifying full-length MHC transcripts by deep sequencing (sorry about the paywall), we hosted a workshop to train other labs on macaque MHC genotyping, Patrick Bohn and Julie Karl presented new macaque genotyping methods at conferences, and Roger Wiseman wrote a review article summarizing our understanding of macaque MHC genetics (again, sorry about the paywall).

The last few months of virus discovery have also been productive. We helped explain the mysterious death of Mahal, an orangutan at the Milwaukee County Zoo. As part of our Kibale collaboration, we helped identify new pegiviruses in people, a novel hepacivirus in black-and-white colobus, novel SIV variants in black-and-white colobus (with a commentary), and divergent hepatocystis lineages in a variety of Kibale nonhuman primates. Michael Lauck, Sam Sibley, and Adam Bailey now have DNA viruses from Kibale monkeys in their sights; expect more news on these viruses by this time next year.

One of the most provocative new developments in the last year has come from our (as yet unpublished...sigh) studies of GB virus C in Kibale monkeys. This dovetails very nicely with research our colleague Esper Kallas is doing with GBV-C in Brazil and we are currently in the process of planning a series of collaborative studies together. Is GBV-C a “Good Boy” virus? An innocent bystander that just happens to be in the blood supply? Something else entirely? It is shaping up like these questions will be a major theme in Adam Bailey’s PhD project.

Finally, the last few months have been great fun. In addition to teaching our undergraduate class on HIV this fall (and getting a nice write-up of it in On Wisconsin!), we hosted a steady stream of visitors in addition to Vincent Racaniello: Jeff Rogers from Baylor, Jack Stapleton from the University of Iowa, and Ron Desrosiers (newly of the University of Miami). Shelby and I had the good fortune of visiting Atlanta and Sao Paulo to meet with collaborators a few weeks ago and I’m really excited to see how these joint research projects develop. In addition, I was delighted to learn that both of my graduate students received training grants this fall. Adam Ericsen is now a Virology Training Grant predoctoral trainee, while Adam Bailey received a Cellular and Molecular Pathology Training Grant.

Not but not least, I’m finally back to full productivity after spending most of the year coping with debilitating migraine headaches triggered by, among other things, blue light emitted from LCD screens and fluorescent light fixtures. If I ever give up virology, it will be to pursue the inexplicable but most certainly real relationship between allergies and migraines. It turns out that my migraines began within a month of discontinuing Zyrtec last winter and persisted until this fall when I began taking Zyrtec again for seasonal allergies. For the better part of the year, I couldn’t use iPads and had to severely limit how much time I spent staring at screens [as an aside, f.lux, which reduces the amount of blue light from computer monitors, single-handedly allowed me to remain productive]. While I’m not one to generalize from anecdotes, I do wonder whether others will experience similar migraine issues triggered by screens in the future. If so, my former technician Alex Blasky has coined the term ‘iGraines’ to describe them.

...and here are a few pictures from the last few months:
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Transitions

It’s a summer of transitions in the lab. Five of our staff are leaving. Three are going to medical school, one is going to graduate school, and one is pursuing a new career opportunity. In addition, a research associate in my wife Shelby’s lab also left to train as a Pathology Assistant. She was one of our first undergraduates back in 2006 and has seven years of accumulated knowledge about how our labs work. We are of course sad to see so many staff move on, but are delighted to see them continue their education and careers.

Next month, AVRL will be welcoming our friend David Evans. David and I have known each other since we were both graduate students training under David Watkins. I’m ecstatic to have David moving to Madison. He is a great friend and will soon be a wonderful colleague and member of our lab neighborhood.

The lab continues to do well. Congratulations to Julie, whose paper on Chinese rhesus macaque MHC genetics was recently published. Senior graduate student Michael has two papers already published this year, with another three in preparation. We have also published papers with our collaborators Brandon Keele and Tony Goldberg. It’s been a busy few months!

More locally, we also helped our UW-Madison veterinary colleagues and the Milwaukee Zoo identify a novel tapeworm that caused the unexpected death of a young orangutan. An article about this collaboration is here.

Finally, this summer I’m teaching a building-wide mini-course on computing. The course uses the excellent “Practical Computing for Biologists” book as its main text. I highly encourage students and researchers interested in my lab’s type of work to invest time to read and understand this book’s topics.

Recruiting

It’s been a whirlwind few months. Last fall I welcomed two new PhD students, Adam Ericsen and Adam Bailey, to the lab. Both are energetic and eager to begin working on their thesis research. If you are reading this as a prospective graduate student, I still anticipate taking only students with three or more years of independent funding this fall.

Research has been going very well. We have sequenced the entire genomes of nearly 20 Mauritian macaques and are currently learning how to analyze these massive datasets. Our work discovering novel viruses in Kibale has led us to a new interest in GBV-C, an apparently harmless virus that seems to offer some protection from AIDS mortality. We were also implicated in studying a virus that could be more ‘deadly, untreatable than Ebola.’ So I can cross ‘do research that could threaten all of humanity’ off my bucket list (note that the article is wildly and irresponsibly exaggerated). We continue to generate lots of MHC and virus sequencing data on the lab’s Illumina miSeq…figuring out how to manage this deluge of data is a pressing challenge right now.

I’m excited to report that several members of the lab are going to be starting medical school in the fall, so I may be hiring at least one research technician this summer. If you are graduating in May and are interested in working for us, please contact me so I can notify you of openings. Note that I am not going to sponsor visas for international scientists for technician positions.

Lastly, I looked at the website’s analytics yesterday. More than 5,000 people visited this site last year, from all over the world. I’m impressed and humbled that people from so many different countries care about what we do.

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Heat waves

It is our typical summer of transitions. Several valued members of the laboratory are leaving to start the next chapter of their careers, while others will be joining the lab. Melisa Budde (biotech startup), Simon Lank (medical school), Adam Ericson (graduate school), Hannah Creager (graduate school), and Brittney Golbach (medical school) are all departing this summer. They will be missed! We recently welcomed two new undergraduates to our team and our first MD/PhD student, Adam Bailey, will be joining this fall.

Scientifically, the last few months have been exciting. Dawn Dudley published a paper describing the use of Roche/454 deep sequencing to study HIV drug resistance. Our projects describing novel viruses in African primates and understanding immune genes of humans and primates have exciting new data. Much of this data has been collected on our Illumina miSeq, a benchtop DNA sequencer that generates 10,000,000 sequence reads per instrument run! Considering we were only studying 96 sequences per run a few short years ago, this has created a new informatics challenge for the lab. Last week I even gave a talk to Illumina about the challenges of working with this type of data in an academic lab. If you had told me a few years ago that I’d be sequencing genomes dengue, HIV, hepatitis C, influenza, and a bunch of crazy novel viruses in my own lab, I wouldn’t have believed you!

A brief note to prospective graduate students. If you are interested in my lab, I strongly encourage you to read my graduate student philosophy and review my CV. Training graduate students is one of the best parts of running an academic laboratory. Unfortunately, the current funding climate is difficult for everyone. We are fortunate to have research support from NIH, but there is a strong possibility that NIH will take steps to more evenly distribute funding in coming years. For more details from NIH’s perspective, read this. In all likelihood, this will cause large labs like mine to downsize. Even though this will negatively affect the productivity of my group, I support the concept of funding more investigators in these difficult times.

A consequence of this probable change in NIH policy is that it will be increasingly difficult to support PhD students on Research Assistantships, particularly in pre-dissertator years when laboratory research time is split with courses and other obligations. Therefore, beginning this fall I plan on limiting rotation opportunities to students who have three or more years of independent financial support.

On the road again

The first few months of 2012 have been incredibly busy for the O’Connor lab. Our collaboration with Tony Goldberg and Tom Friedrich to discover new viruses brought me (along with graduate student Michael Lauck) to Kibale, Uganda in late January.

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While we were off in Africa, lab members were busy in the lab. We were involved in three recent publications:

Johnson, Z. P., R. D. Eady, S. F. Ahmad, S. Agravat, T. Morris, J. Else, S. M. Lank, R. W. Wiseman, D. H. O’Connor, M. C. Penedo, C. P. Larsen, and L. S. Kean. 2012. Immunogenetic Management Software: a new tool for visualization and analysis of complex immunogenetic datasets. Immunogenetics 64:329-336:

Lauck, M., M. V. Alvarado-Mora, E. A. Becker, D. Bhattacharya, R. Striker, A. L. Hughes, F. J. Carrilho, D. H. O’Connor, and J. R. Rebello Pinho. 2012. Analysis of Hepatitis C Virus Intra-Host Diversity Across The Coding Region by Ultra-Deep Pyrosequencing. J Virol

Mudd, P. A., A. J. Ericsen, B. J. Burwitz, N. A. Wilson, D. H. O’Connor, A. L. Hughes, and D. I. Watkins. 2012. Escape from CD8+ T Cell Responses in Mamu-B*00801+ Macaques Differentiates Progressors from Elite Controllers. J Immunol

…with several more in the pipeline.

We were also saddened by the departure of Dr. David Watkins, a longtime mentor, colleague, and friend, for the University of Miami at the start of 2012. The entire lab wishes David the best of luck with this new chapter of his career. Two of David’s staff members elected to stay in Madison, so Dr. Matt Reynolds joined our lab in February and Adam Ericson joined our lab briefly to finish his MS thesis.

Spring will bring more interactions with other HIV labs. Melisa Budde presented recent data at the Conference on Retroviruses and Opportunistic Infections, while I presented some of this data at the Palm Springs Symposium on HIV/AIDS. In about two weeks, Shelby O’Connor and I will visit our colleagues in Brazil and participate in a short course on HIV pathogenesis. Busy times all around!