Notes from the Lab
March 4, 2014
Reinventing bone marrow stem cell gene therapy
Almost a year ago, the FRIENDS OF DOERNBECHER funded our research project to develop "new and improved" gene therapy vectors that would provide enhanced safety for genetically modifying bone marrow stem cells.Santhosh and Natalya published a substantial part of that work this past month in the Scientific Journal Nucleic Acids Research. The journal article is nothing short of a 10-page tour-de-force in molecular biology to illustrate the ability of the new anchoring episome lentivector to persist without integrating into the cell's chromosomes. Santhosh had long favored the nautical themes (anchor!) for his lab meeting update slides on the project and that seemed to resonate with the journal reviewers who liked the new addition to vector nomenclature:"anchoring non-integrating lentivector, anILV ".
What's the big deal? The accidental integration of conventional vectors into the stem cell chromosomes can lead to skewing of the bone marrow stem cell pool and, in the extreme, leukemia. aniLV-episomes are anchored and stick around each dividing daughter cell, but they do not seem to integrate. The article also shows the power of teamwork, as Natalya and Santhosh worked together, complementing each other's expertise to complete these studies.
What is next? We will use the anILV vector to improve gene transfer to stem cells from Fanconi Anemia mice and demonstrate that episomes persist in the rapidly dividing bone marrow stem cell pool where they can genetically correct the hematopoietic failure that plagues FA patients.Episomes rule!
January 17, 2014
Noah receives a grant from the National Cancer Institute
In what we hope will be an auspicious beginning to the new year, Noah received some very good news from the National Cancer Institute when word came that his training grant was funded (a multi -year National Research Service Award, NRSA). At a time, when funding remains tight and the competition is strong, Noah’s proposal scored at an astounding 8% in his study section (the lower the number the better). The enthusiasm came through in the written critiques Noah had received from the scientific review committee, pointing out the overall strength of the applicant, project and OHSU as the scientific environment for the proposed work. The award represents a strong vote of confidence and validation for Noah’s hard work over the past year. A consummate teamplayer and problem-solver, never shy to embrace an argument, the committee saw in him a very promising scientist.
We agree, but someone else was more prophetic: The pic of a shipment received from collaborators 2 years ago. Congratulations Professor Hornick!
December 23, 2013
Ashley Kamimae-Lanning successfully defends her PhD-Thesis
A very big day, five years in the making: On December 18 Ashley successfully defended her Thesis: “ Programming of the fetal Hematopoietic Stem and Progenitor Cell Compartment”. In front of friends, family (with parents watching via video conference) her undergraduate research advisor, OHSU students and faculty she gave a polished presentation and navigated the subsequent questions with ease and confidence. Evenings and weekends of hard work pay off as the leaves behind the student days to receive her PhD. Much was accomplished during those five years: Lab meetings, conference presentations, grants, awards, and papers published. (And her first passport for international travel). Much more along those lines is to follow as she begins her stint as a post doc in the lab to finish up work and publish the remaining studies based on her thesis work. For the time being, well-deserved vacation and the holidays loom. As of January 2014: Welcome, Dr. Kamimae -Lannning. (on the pic: Ashley and Peter - proud and relieved)
November 15, 2013
Kelsie Storm is the 2013 Neerhout Fellow
Dr. Robert Neerhout is counted among Oregon’s legendary Pediatricians. Not many of us had the privilege of working with him, but Dr. Larry Wolff, who counts Dr. Neerhout among his mentors, reminds us annually during his introductory remarks at the award presentations how high the bar was set for all-around excellence in Pediatrics at Doernbecher. And even in a competitive group of peers, it comes as only a small surprise that Kelsie who joined us in July is this year’s Neerhout Fellow. This is a remarkable vote of confidence for Kelsie who in accepting the award noted her gratitude to Dr. Susan Lindemulder and Dr. Linda Stork (Neerhout Professor of Pediatrics) - her clinical mentors.
To top off a spectacular week, her review article on hematopoietic stem cell expansion appeared in “The Hematologist”.
We could not be prouder! The picture? Digging clams; in style!
July 17, 2013
Jianya wanted to check out the ziplines in the Gorge, Noah prefers rock-climbing, but everyone agreed on the picnic. So we decided to spend our retreat at the Coast: Clamming in Netarts Bay.
We were joined by Forest and Katy, the hardest working students on campus and spent the day digging in the sand. In the process we seem to have collected all the shellfish that our licenses would allow. Strategies for success differed in interesting ways, as Kelsie teamed up with Forrest for what can only be described as an “open pit” strategy, whereas Katy insisted on a more organic approach using only her hands. Much the same can be said for our picnic where levels of preparedness ranged from chicken for the grill to a multi-pot assembly to steam the clams (Strong leadership, Shelton!).
If ever you find yourself ready to clam and without equipment: Kelsie learned that they rent shovels at the marina (who would have thought you can rent one??).
Great weather, great group and GREAT fun. What to do next year???
May 23rd, 2013
Friends of Doernbecher Grant Awarded !
WE RECEIVED WELCOME SUPPORT FOR OUR GENE TEHRAPY RESEARCHOnce a year the Friends of Doernbecher solicit grant proposals from pediatric researchers across OHSU. For many years these seed grants have provided crucial support and start up funds to develop new ideas and generate preliminary data for NIH grants. For 2013, the Friends decided to substantially increase their total funding. Good news! After all was said and done (21 applicants and six finalists who presented to a review panel) we were fortunate enough to be among the lucky four recipients for this year’s awards.
This generous support ($60,000) will help fund our gene therapy project as we develop non-integrating lentiviral vectors for bone marrow stem cell therapies. We are grateful to the Friends and all those that helped to make it happen. Congratulations Santhosh and Natalya. Your hard work and dedication paid off !
February 11th, 2013
9th Annual Fanconi Anemia Run/Walk
Another Year's Run For a Great Cause!
In a bit of a Valentine's Weekend tradition we enjoyed unseasonably dry and sunny weather for the 9th Annual Valentine's day Run/ Walk. Hundreds came, bringing awareness and energy to the Portland Waterfront, complete with bagels, hot chocolate and some funny costumes. Meeting friends and bringing families all for a great causes: FA research. Not to be missed the transformation of the course from gravel, mud and puddles to the beginnings of the OHSU waterfront campus and the new OSU Life Sciences building. Natalya organized and captained a team this year, with family to boot.
January 25, 2013
Amy completed her post-doctoral training ! With a laundry list of accomplishments and after 6 years of hard work Amy is moving on. During that time, she hit all the highlights one would hope for: First author publications, 4; authorships total, 9; training grants, 3; travel grants, 2; conference sites travelled to: Seattle, San Diego, Boston, New Orleans, Atlanta, San Francisco,… Interns trained, …lost count;. Amy directed the Department of Pediatrics Internship Program for 5 years from its inception and her skills and can-do attitude will be sorely missed around here.
Fortunately, she is not moving too far, taking a position as Lecturer in the Department of Surgery at OHSU where she will work with SueEllen Pommier.
May we have predicted her success? Apparently her cousin did in having her lab coat embroidered- 6 years ago: Super Star!
October 5, 2012
Annual Scientific Meeting of the Fanconi Anemia Research Fund
Once a year the FA research fund convenes their scientific meeting and this year we travelled to Denver.With over 200 international participants the meeting was as well attended as ever. The schedule was packed with educational opportunities from Thursday to Sunday morning. Particular highlights were the very encouraging updates on the stem cell transplantation experience and a scientific session on different methods of stem cell expansion. A new format was the point- counterpoint session featuring discussants addressing pros and cons of androgen use as well as radiation containing conditioning regimen for transplantation.
My favorite; a session devoted to the etiology of bone marrow failure with further evidence for a developmentally programmed, in utero onset.
Alas, no gene therapy this year!
June 21, 2012
Summer - Internship time!
We have had laboratory interns for most of the past summers and will host three this year. Nothing like inquisitive young minds to push research forward. No slackers here!
Kyle Lenz decided to rejoin us after his experience last spring when he spent his spring academic quarter in the lab. He just completed his sophomore year at Dartmouth and will work with Jianya and Noah on the leukemia vesicle project.
Karen Huan just graduated from the IB program at Southridge High School. She has been working with us as a part time lab aide for the past 6 months and decided to work on a project with Amy and Santhosh before heading off to Williams College.
Basma Saadoun is one of this year’s OSLER TL-1 Summer research Award recipients. She will pursue studies funded through the program to study the effects of high fat diet on the developmental programming of hematopoietic function. This project is in conjunction with the laboratory of Dan Marks. All three will pursue their research
February 29, 2012
Natalya's Poster at OHSU Rare Disease Day 2012
Natalya joined us last fall and has been working hard with Ashley on the Fanconi Anmeia-Fetal Hematopoiesis project. Tasked with carrying on protein array work, but also setting up PCR studies on fetal liver expression of key hematopoiesis regulators, she made several important observations. We were all excited to help her prepare a poster including her data and the first ever OHSU Rare Disease Research Day was a great venue to present those findings. Designed as session opener, the poster session was well attended and Natalya stood her ground to inquisitive questions. She will continue her work in developing an immunohistochemistry protocol for this project and has taken a lead in expanding our mouse colony. Many more presentations to come– and not just on leap day !
Check out program links and highlights of Rare Disease Research Day here: http://ozone.ohsu.edu/blogs/somresearchvoice/2012/03/05/standing-room-only-at-the-rdrc-conference/
February 12, 2012
What to do on a rainy Sunday morning in Portland in February ?
The 8th Annual Valentine Day Run is a pretty good place to start. Twelve hundred believers in FA research showed up and $46,000 were raised. OHSU had a strong presence and it was fun to see friends and community come together to support the cause.
Ashley’s third year (I think) and eight for me. We will have to work on growing the team and upgrade on our gear. Not much a fan of bee costumes (I counted three runners in those), maybe it’s time to get personalized hoodies, like Maureen.
December 6, 2011Still unpacking boxes from his move to Portland, Santhosh C. Verghese joined us this week. He brings experience and critical expertise in retrovirology and vector design to the lab. Santhosh and his wife and son relocated from the Washington DC area, where he most recently worked at the NIH. Santosh has already been counseled not to take the current Portland sunshine for granted. Word on the street is, Santhosh has plans to rediscover his bike legs. WELCOME !!
October 10, 2011
Exciting news this last week as Ashley, Noah and Michael had their abstract submissions accepted for presentation at the December Annual Meeting of the American Society of Hematology. Along with co-authors, they worked hard over the summer months to complete (...and repeat, and repeat...) their experiments.
- Ashley N. Kamimae-Lanning, Tae Hoon Ha, Amy M. Skinner, Thomas B. Russell, Peter Kurre Developmental defects in hematopoiesis in a mouse model of Fanconi Anemia.
- Noah Hornick, Jianya Huan, Jeffrey W. Tyner and Peter Kurre. Flt3 Kinase Regulates Microvesicle Transfer of miRNA Between AML and Stromal Cell.
- Michael Layoun, Amy M. Skinner, Jianya Huan, Peter Kurre. Exosome trafficking of BCR-ABL oncoprotein promotes the IL-3 independent proliferation of bystander cells.
All three will be busy preparing their presentations of the next few weeks and we are looking forward to attending the meeting in San Diego. http://www.hematology.org/meetings/annual-meeting/
Much deserved recognition and a sun break in the upcoming rain season!
July 25, 2011
With several people having recently joined, we decided to take some time away and have a lab retreat visiting Ape Cave and Lava Canyon on the slopes of Mount St. Helens. Rewarded by sunshine and just enough clouds to enhance Jianya's photos we took a guided tour of the Lavatubes. Amy turned out to be a skilled naturalist and promptly spotted the elusive gyrlloblattid (below) in the cave. (Proposed as the new lab mascot by Thomas). Noah brought no fewer than 6 lights only to find that most of them had exhausted batteries. Michael had hoped for some serious spelunking, but left the cave without any lost treasures.
After more than an hour in the cave at 42 F, we were ready for our picnic, greatly enhanced by Lauriel's Mojito's and A LOT of food. Finally a hike through the Lava Canyon and Ashley's cupcakes to complete the day! Lots of fun.
Joining us for the summer - and on this trip - were Lauriel, incoming PMCB student, Michael Layoun (MS1) and Tae Ha (MS2)
June 8, 2011We recently welcomed Jianya Huan PhD to the team. Jianya brings extensive experience in Molecular Biology and Protein Biochemistry to the group and will help us expand our research in microvesicle biology. He received his PhD from Oregon State University and was s a long -term member of the OHSU Neurology Department - Multiple Sclerosis Study Group. Jianya will provide us with valuable research expertise in immunology and serve as a great teacher to others.
May 12, 2011
¡ Hola Ashley !
Ashley just received word that she was named a 2011 Tartar Trust Fellow. The award will allow her to present her research project at the annual Fanconi Anemia (FA) Research Conference. A US-based conference in most years, except when the organizers decided to hold this year’s event in Barcelona, Spain.
Ashley has worked hard on her experiments understanding the developmental origins of bone marrow failure in the Fancc mouse model. Her work highlights a resurgent interest in the developmental hematopoiesis in the FA field as part of an effort to gain a more fundamental understanding of FA biology. Knowing more about the onset of hematopoietic failure and to what extent stem cell exhaustion is of pre-natal origin will have implications for diagnosis and perhaps treatment. It would also provide a much-needed perspective to complement research into induced pluripotent FA patient stem cells.
As for her Barcelona presentation..., it looks like she will have plenty of practice opportunity this week and next. She will be giving oral presentations at the student research forum and also at the Cell & Developmental Biology departmental seminars, respectively.
What a week. Well-deserved recognition of her dedicated work in the lab and the prospect of some exciting travel coming up this October.
April 13, 2011
LESS IS MORE!
Who would have thought what effort it takes to get rid of a little oxygen!
Oxygen partial pressures in most tissues are well below ambient conditions and those commonly used in tissue culture incubators. This has long been recognized as a limitation to cancer and hematopoiesis research. Hypoxia is also a key feature of the hematopoietic niche and plays a principal role in maintaining the stem cell pool. Hypoxia in the tumor microenvironment helps promote tumor vascularization and leukemogenesis is intricately linked to low oxygen in the bone marrow. Even Fanconi anemia progenitors show improved colony formation in low oxygen conditions.
Sounds like a great resource for our research program ? We certainly think that the ability to culture and (with some funding for a microscope…) seamlessly analyze cells under these conditions will substantially enhance our research program capability and provide new insight in stem cell and cancer biology.
The hypoxia chamber will be available to OHSU stem cell center and pediatric research faculty as a shared resource.
While we are finishing the final install and look forward to taking the chamber into operation, we want to thank Qianyue Wang and J-B Roullet, PhD, for their help getting this awesome piece of equipment up and running.
April 5, 2011
Welcome Kyle !
Kyle Lenz has joined the lab for a spring semester internship. Kyle is a native of Salem, Oregon and graduated as valedictorian of his class from West Salem High School. He subsequently enrolled at Dartmouth College in New Hampshire where he is currently finishing his sophomore year.
Kyle has a long standing interest in science and is participating in the Howard Hughes Undergraduate Training Program at Dartmouth where he works in the lab of Dr. Jay Dunlap and Dr. Jennifer Loros. Over the past year he has conducted research on the effects of DNA damage on the mammalian cell and the role it plays in the circadian rhythm of an organism through a mouse embryonic fibroblast model. Kyle plans to continue this work in the Dunlap/Loros Lab over the course of the next year, before eventually writing a thesis. While here, Kyle will participate in work on understanding intrahematopoietic cell fusion. He will specifically work on developing high resolution melting temperature PCR protocols for SNP analysis in cell fusion products and will look for lineage ambiguity in cells from transplant recipients.
We are excited to have Kyle join the lab and look forward some exciting science !
March 17, 2011
Happy St. Patrick’s day!
The St. Baldrick’s Foundation has awarded a St. Baldrick’s Summer Fellowship Grant to the OHSU Department of Pediatrics Summer Internship Program!
For the past 4 years Amy Skinner, Ph.D. has directed this Internship program to foster science education at OHSU by matching undergraduate and highschool interns with Pediatric Faculty Mentors for a summer research experience. Under her guidance, the 10-week summer program promotes science through faculty seminars, workshops, journal clubs and peer group networking.
Always on the lookout for ways to further enhance the program, Amy initiated an institutional application to the St. Baldricks Foundation, championed by Department Chair H. Stacy Nicholson, M.D., MPH. Now Doernbecher will join a group of six elite Children’s Hospitals in the nation that currently receive the award Duke, Columbia, Rainbow & Babies in Cleveland, among them. The generous $5,000 fellowship grant will specifically support medical students working on pediatric oncology research the summer between the first and second year of medical school. This grant allows for a summer fellow stipend and expenses.
Training the next generation to make a difference!!
February 24, 2011
Congratulations Amy !
The OHSU Knight Cancer Institute and U.S. Bank have awarded the 2011 US Bank Cancer Research Development Award to Amy Skinner.
The annual award recognizes promising young OHSU investigators and supports their important work in cancer research. In selecting Amy from a field of uniquely talented colleagues, the Award Committee recognized Amy’s talent, drive and commitment. Her project aims to understand the role of chromosomal changes in bone marrow cells and whether those changes are the earliest harbingers of cancer. The innovative work was conducted in close collaboration with the lab of W. H. Fleming and was presented in part at the 2010 Annual Meeting of the International Society for Stem Cell Research. Amy’s discussion of her important observations at the December 2010 Meeting of the American Society of Hematology (ASH) was subject of strong interest during the meeting and rewarded with an ASH Travel Award.
The US Bank Cancer Research Development Award was awarded during a luncheon with US Bank and OHSU Knight Cancer Institute leadership.
Pictured Left to Right: Malia Wasson, U.S. Bank President, Peter Kurre, MD, Amy Skinner, PhD, and Brian Druker, MD
February 13, 2011
Annual Valentine's Day Fanconi Anemia Run/Walk
For the seventh year running Peg Padden has hosted the Fanconi Anemia (FA) Valentine's Run at the Portland Waterfront. This great grass roots community event is held annually to benefit research into causes and treatment of Fanconi Anemia, a rare inherited illness that results in the loss of blood forming cells and an increased risk of developing cancer. Testament to Peg's talent in motivating people, the event has grown to attract over 1000 participants this year and will contribute nearly $47,000 to the Fanconi Anemia Research Fund effort to help patients with this illness. As an added attraction the first -ever Adult FA patient meeting was held on the same weekend!
Joining FA patients, other researchers and friends, Ashley, Peter and their families helped spread the word. Ashley has actively researched the roots of bone marrow failure and stem cell loss in this disease as part of her PhD thesis project. She and Jared were repeat participants and completed the 12k walk. Peter and family took the 5k shortcut.