Congratulations, Monika!

Many congratulations to Monika, whose publication from earlier work in the Soderling Lab on medulloblastoma migration has recently been released for early electronic publication in the Journal of Neuro-Oncology.  This thoughtful paper on mechanisms of medulloblastoma migration also takes a look towards pharmacological inhibition, a step towards addressing leptomeningeal metastasis. 

Rebecca and Sada Tarshis Endowed Professorship

It is an privilege and honor to be a steward of the Rebecca and Sada Tarshis Endowed Professorship.  These two sisters came from a modest background as children of immigrants from Russia, yet by building careers and living well, though judiciously, created a legacy that continues to benefit the Portland greater community.  I hope that through the work of our laboratory and the Pediatric Cancer Biology Program that we will meet the example of bringing forth tangible change and contributing to the greater good, particularly with respect to outcomes for metastatic childhood cancers. 


-- Charles  
  
[ above right:  Charles with Elaine, who is holding 'the chair'.  For the SOM Newsletter article, click here. ]
  

Visiting Scientist, Tohru Hosoyama

We were honored to have lab alumnist Tohru Hosoyama visit our lab in Portland this past week.  Tohru is now a fellow in the laboratory of Dr. Masatoshi Suzuki at the University of Wisconsin in Madison.  Tohru is no doubt a rising star to watch in the muscle stem cell biology field.  
  
[ above right: Tohru with lab members Monika, Charles & Jinu ]

Welcoming Guangheng !

We are excited to welcome surgeon-scientist Dr Guangheng Li the Keller laboratory.  'GH' received his M.D in 1996 from Henan Medical University and his Ph.D in 2002 from the Shanghai Second Medical University. As a member of the Stem Cell Research Center in the Department of Orthopedic Surgery at University of Pittsburgh, GH authored or co-authored numberous tissue engineering and stem cell studies that have been published in the Journal of Tissue Engineering, Journal of Bone and Mineral Research, Nature Biotechnology, and Arthritis and Rheumatism. His research has focused primarily on using gene therapy, skeletal muscle stem cell and protein therapy to improve bone healing and delay the process of joints disease.  In the Keller laboratory, GH will extend these interests to the study of activated muscle stem cells and muscle cancer (rhabdomyosarcoma). 

Pediatric Cancer Biology Strategic Planning Retreat

We thank the leadership and key members of the OHSU Division of Pediatric Hematology-Oncology, as well as our partners from the Doernbecher Children's Hospital Foundation for attending this Fall's first annual strategic planing retreat for the OHSU Pediatric Cancer Biology Program.  The retreat met yesterday at Skamania Lodge in the Columbia River Gorge.  The event was moderated by Dr. Cory Hallam, Director of Commercialization Alliances and Innovation as well as the Center for Innovation and Technology Entrepreneurship (CITE) at the University of Texas at San Antonio.  It was a very productive day, with the only caveat that we were indoors nearly the entire time, whilst it was a beautiful day outside. Still, it was a tremendously valuable activity and will lead to a highly specific strategic plan to be generated in the coming weeks. 

  
[ credits and thanks to Dr. Linda Stork for the Gorge photo ]
  

Hyundai Hope on Wheels funds Rhabdomyosarcoma study

We are grateful to the Portland area and national Hyundai dealers who so graciously fuel the Hyundai Hope on Wheels program to fund childhood cancer research across the nation.  Our laboratory yesterday received a generous award of $100,000 to study the response of alveolar rhabdomyosarcoma to growth factor inhibitors... and to determine the mechanisms by which such strategies might be improved to prevent relapse and inhibitor resistance.  We are all also very humbled by rhabdomyosarcoma patient, Josh Flanery, who took his time to talk with the group about his own experience with adolescent and young adult cancer.


YouTube video:    http://www.youtube.com/watch?v=VxOlgtbd5Z0 
  
Fox News coverage:  http://www.kptv.com/local-video/index.html?grabnetworks_video_id=4353023 
  

Exciting New NCI Award

We are thankful to be one of a handful of recipients of an R01 supplement exceeding $200k in response to the Carolyn Price Walker Act.  This award to our laboratory and the Northwest Sarcoma Foundation is meant to increase awareness of the improved outcomes of childhood cancer patients when treated at specialized, multi-disciplinary centers.  We also have a project to increase awareness of the value of biopsy samples for scientific research when tumors grow despite treatment.  Many thanks to the great number of people on the team at Doernbecher Children's Hospital, Melissa Hill at the Northwest Sarcoma Foundation, and Nancy Goodman of Kids vs Cancer for making this possible.   

COG Fall Meeting

This past week was the Children's Oncology Group Fall meeting.  Normally, the COG meets twice a year to discuss design and results (when available) of the latest clinical trials.  This was a particularly special meeting, in that founding COG Chair, Dr. Gregory Reaman, was recognized for his phenomenal legacy of work with COG & CureSearch, and physician-scientist Dr. Peter Adamson took the leadership position moving forward.  This meeting was well attended by pediatric oncology medical caregivers and the public alike.  Our lab's contributions were a rhabdomyosarcoma presentation to the Soft Tissue Sarcoma Biology Special Session, as well as chairing (with the help of Maryam Fouladi) the CNS new therapeutics session.  
  
[ above right:  Charles and Ross Vick, advisory director member of QuadW, discussing sarcoma research ]

Legislation and Childhood Cancer

Groups like CureSearch, foundations and individuals approach childhood cancer advocacy through hard work in lobbying for executive and legislative initiative that improve the research and care of childhood cancer patients.  One example is that September is "Childhood Cancer Awareness Month" by Presidential Proclamation.  Nancy Goodman is a childhood cancer parent and founder of KidsvCancer.org who regularly lobbies on behalf of childhood cancer causes.  Another advocacy group for increasing drug availability for cancer patients is the Abigail Alliance.  These groups certainly deserve our thanks and support in their efforts.  
  
  
  
[ 9/15/10   For a touching story about a little girl named Joanna whose memory is bringing awareness and rallying a community around childhood cancer patients, click here.  ]
  
[ 9/16/10   See Nancy Goodman's testimony before the House at  http://www.kidsvcancer.org/pediatric-cancer-caucus/ ]

   

speeding the pace of Phase I studies

We'd like to acknowledge nurse Rae Acosta who is coordinator for the Pediatric Oncology Phase I program at Doernbecher Children's Hospital, with whom we team to design preclinical trials that address special populations of pediatric cancer patients most in need of drug development.  Dr. Suman Malempati is overall leader of this COG-affiliated Phase I program, and it is the cross talk that we develop with Rae and Suman that makes what we do in the research lab seem all the more tangible. 
   
[ above right:  Jen (left) and Rae (right) next to some new equipment in the lab ]
   

The Seattle - Portland Connection

We are grateful to the basic scientist and clinical researchers at the University of Washington, Seattle Cancer Care Alliance and the Fred Hutchinson Cancer Research Center for meeting with our OSHU team (Suman Malempati, Chris Ryan and I) to discuss areas of synergy between our research programs.  We found strong common interests, particularly in the areas of (1) understanding how medulloblastomas grow and spread, (2) defining the basic biology of the differentiation defect for rhabdomyosarcoma and (3) translating recent studies of adolescent and adult sarcoma biology to clinical trials.  The opportunity to explore immunotherapy for sarcomas is especially strong, too.  We are thankful to the laboratories of Dr. Jim Olson, Dr. Stephen Tapscott, Dr. Michael Jensen and the clinical trials researchers Doug Hawkins, Robin Jones, Eve Rodler - and especially surgeon-scientist Chappie Conrad, for taking the time to explore and initiate these dual city collaborations in the Pacific Northwest.  
    
Charles
  

Tissue Banking - Demystified

A question sometimes asked is how research can be advanced, and contributing tissue to a tumor bank for research is a key element (money, yes, is nice... but high quality tissue from patients with tumors for which little is know is more valuable).  And if it can be put in a gentle way, tumor tissue from the patients that researchers and clinicians so far have failed is the most valuable.  That is, tissue from patients with relapses... even post-mortem biopsies from patients that have failed our best treatments.


How does one enroll to give tissue? In the case of soft tissue sarcomas, the Children's Oncology Group (COG) has had a tumor bank protocol called "D9902" open since March 1999.  The consent form for this study is usually presented to families at the time a child is diagnosed and is being considered for a COG treatment study.  Most people think of D9902 as a study for collecting tissue from the original untreated tumor, but... the protocol does already allow tissue to be collected from biopsies done at the time of relapse, as well as tissue taken after death (autopsies, partial autopsies and post-mortem biopsies).  In practice, relapse samples rarely are collected (there are practical reasons not to subject children to extra procedures).  Post-mortem samples are scarce... maybe none, with recent notable exceptions.


Where does the tissue go?  well, a really good tumor bank!  The COG contracts the Pediatric Cooperative Human Tissue Network (pCHTN) to store COG sample studies.  Their Director is Dr. Nilsa C. Ramirez, and she and the Biopathology Center for the pCHTN are at the Nationwide Children's Hospital in Columbus, Ohio.  Nilsa succeeds the late Dr. Stephen Qualman, who himself was taken by pancreatic cancer.  Dr. Qualman was a leader in rhabdomyosarcoma pathology research, but Nilsa keeps this tradition in sarcomas strong, and she was recently joined by rhabdomyosarcoma researcher Dr. Peter Houghton who is building an exciting pediatric cancer research program at Nationwide.


What happens with the tissue?  It gets used, hopefully!  Dr. Stephen Skapek at the University of Chicago leads the Soft Tissue Sarcoma Biology subcommittee of the COG.  Researchers send the pCHTN/COG applications to use the tissue. The applications are reviewed by Steve and others on his committee (such as myself).  If the study looks promising, a few samples are sent.  If the researcher shows promising results, many more samples can be sent.  In fact, for the best studies we even consider, "emptying the bank".  (important notes:  the researchers only have de-identified samples... they won't know each patient's name.  Also, statistical rigorousness is another important judging criteria for proposed studies).  


How much does it cost?  In theory, it shouldn't.... the tissue collection kits are meant to be a part of the existing COG D9902 protocol.  However, there have been cutbacks in what the NIH/NCI gives COG for its studies. If there were a sudden 'flood' of samples, the pCHTN and I estimate it would cost  $150 total (70 for the kit, 30 to ship the kit to the child's hospital, 50 to ship it back on dry ice).  I've talked with a few foundations on whether they'd sponsor kits, and while we don't have any definite commitments, I think if the need arose we could find a way that patients wouldn't need to use their own money to contribute to research through the tumor bank.


I hope this helps with some of the questions arising lately. Feel free to comment on this blog or email me for more information.  


Sincerely,
Charles




   

Welcoming Nicolle!

We are proud to welcome Dr. Nicolle Hofmann to the Keller laboratory as our 2010/2011 Scott Carter Foundation Fellow at OHSU.  Nicolle will be pioneering an osteosarcoma therapeutics study between OSU (Corvallis) and OHSU (Portland).  To this project Nicolle brings a background in plant genetics, which is probably very appropriate for certain kinds of therapeutics we will be exploring.  


Nicolle's bio, in her own words:


" I received my B.Sc. in Animal Sciences at the University of Illinois. After taking a couple years off from school to work as a research assistant in the Nutrition and Food Science laboratory of Dr. John W. Erdman, I went on to pursue a Ph.D. in Plant Breeding and Genetics. Since completing my Ph.D., I have held two post-doctoral positions, one in the Soybean Genomics and Improvement Laboratory at the USDA in Beltsville, Maryland and one in a plant metabolic engineering laboratory at Virginia Tech in Blacksburg, Virginia. Now that I am here in Portland, I am very excited to enter a very important area of research in the Pediatric Cancer Biology Program at OHSU."


Welcome, Nicolle!
   

Scott Carter Foundation Big Show! and Golf Tournament

Jinu and I were privileged to attend and participate in the Scott Carter Foundation fundraiser events this weekend in Tulsa, Oklahoma.  This is an all-volunteer driven two part event, the Big Show dinner and auction, and the Indian Springs Golf Tournament.  It was my pleasure to meet the numerous proactive benefactors of the SCF in Tulsa, including some special parents of childhood cancer survivors including Amy White, a tireless advocate of families in her role as Pediatric Oncology Coordinator of the Oklahoma Family Network.  In its 17th year, this event exemplifies the commitment of a Scott's Family, and his community, to honor his memory by building a stronger foundation of research in childhood cancers. We are grateful that Jinu could be the 2009/2010 Scott Carter Fellow at OHSU.  
  
Charles


[ above right:  John Grant, Paula Carter, Jinu Abraham ]
[ below right:  Jinu Abraham, Cason Carter, Charles Keller ]
   

an informal word on our lab's research

Our laboratory focuses on long term and near-term treatments for the childhood muscle cancer, rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma. To say long term, we mean basic science investigation of how these tumors work – such things as what kind of normal cell gives rise to one particular kind of cancer. And in saying near-term, we mean finding molecules in these cancers to directly turn off or turn on by drugs so that the tumor stops growing. Behind both approaches are some rather exciting genetically-engineered mice… modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. Then the tumor can be followed to see how it grows and spreads… even to test a treatment to see whether the tumor growth can be reversed. That these mice have normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

While this use of mouse models makes our lab slightly unique, our greatest asset is that we have a very multi-disciplinary team. Biomedical engineers for building and operating imaging and diagnostic instruments, biochemists for understanding the molecules, molecular biologists and electrical engineers for understanding how tumors express genes in certain ways, and me (the board-certified pediatric oncologist) helping bring it all together in a focused way. Sometimes we venture beyond the ordinary, such as the use of 26¢ fertilized quail eggs (instead of mice or petri dish experiments) to study anti-cancer drugs. That last project is one graciously sponsored by the Alex’s Lemonade Stand Foundation. We’re even the first to work with the National Cancer Institute’s Pediatric Preclinical Testing Program to try exciting new drugs right out of the pharmaceutical development pipeline in genetically-engineered mouse models of childhood cancer.

I’d like to think that tangibly better treatments for rhabdomyosarcoma and medulloblastoma can be found in a matter of years, instead of tens of years. I go to a fundraiser golf tournament for the Scott Carter Foundation every year. They sponsored my research training in Mario Capecchi’s lab years ago, and now sponsor our pediatric cancer researcher in training, Nicolle Hoffman. Standing at the 18th hole every year, I get the same question about every 5 minutes, “Doctor, do you have anything new for these kids yet?” These questions led my lab to put a heavy emphasis on therapeutics about 4 years ago. As a result, we’re finding drug targets, as well as drugs to hit those targets that are less inclined to result in relapse for our patients (ok – yes, it’s just mice so far, but I also am a member of the Children’s Oncology Group committee that designs COG trial for rhabdomyosarcoma).

What's on the horizon?  A lot!  In moving to OHSU in Portland we're now teaming with Dr. Brian Druker to develop personalized targeted therapies (of the non-chemotherapy variety) for children with cancer.  Our results can move faster than ever from the bench to the bedside with the COG Phase I pediatric oncology program here at our Doernbecher Children's Hospital, and with the leadership opportunity of building a de novo Pediatric Cancer Biology Program at OHSU, there's tremendous potential to build a focused team of laboratories that share a common goal of doing the best research and moving making results relevant to patients in the here and now.

Where there is a will, there is a way. Change can be tangible.  And we are accountable.

Charles Keller, MD
keller@ohsu.edu

OSU College of Veterinary Medicine

We thank Dr. Bernard Seguin (oncological surgery) and Dr. Shay Bracha (oncology) for meeting with us today to discuss the intersection of childhood and companion pet clinical trials for cancer.  The specialized facilities at the Oregon State University College of Veterinary Medicine are truly outstanding, and represent a strong resource for partnerships in developing new treatments for soft tissue and bone sarcomas of childhood and adolescence.  


[ above right:  Jinu, Bernard, Charles & Elaine at OSU ]
[ note: neither Ducks or Beavers were harmed in the pursuit of this collaboration ]
  

The “Creating Hope Act of 2010” S.3697

This important proposed bipartisan legislature by Senators Sam Brownback (R-KS), Sherrod Brown (D-OH), and Al Franken (D-MN) would encourage pharmaceutical companies to develop new drugs for rare childhood diseases, including cancer.  Essentially, the pharmaceutical companies would receive a voucher to expedite FDA approval.


For more details, visit Nancy Goodman's website for KIDS V CANCER.     
  
  

Suresh's Cover!

Congratulations to Suresh whose multi-modal molecular imaging is the cover of Molecular Cancer Therapeutics ! The broader description of this study is that we can now investigate rhabdomyosarcoma tumor cell interactions with the blood vessels and the immune system... using optical imaging, and without the interference of, well, hair!  


Many congratulations again to co-first authors Bev and Marcia, as well as Suresh!
  
[ For the abstract, click here ]   
  
  

Jackson's Ride the Gorge

This past weekend we had the good fortune to participate in Jackson's Ride the Gorge in Hood River, OR.  This fundraiser honors the memory of 12 year-old Jackson Hill who battled osteosarcoma and inspired the beautiful ride through the Columbia Gorge.  The money raised is used for increasing awareness and supporting research for sarcoma, a cancer of the connective tissue.  We found ourselves humbled by the number of people who rode (300!) or volunteered (over 70!) to make this event happen and were delighted to have the opportunity to provide aide at rest stops and at the finish line alongside them. 

It is safe to say that we have been moved by the enthusiasm and dedication of all involved and intend to participate (we hope as riders!) in the years to come.

  

(photos and text by Elaine, who with Audra volunteered at The Dalles support station)  

    

Hyundai Hope on Wheels Award to Doernbecher & the PCB Program

Our research team in the Pediatric Cancer Biology Program is grateful for this opportunity to further childhood cancer research on behalf of Hope on Wheels, Hyundai and their dedicated employees.  The effect of Hope on Wheels can be tangibly seen across the nation, not only through the distinctive handprint cars, but through the innovative research that has been sponsored at so many academic hospitals and centers. 

We are honored to have this chance to do our part.
     
    

for the KATU TV story, click here .

Congratulations to Sachiko!

We are excited that Sachiko's cell and biochemical studies for IGF receptor inhibition in medulloblastoma have been accepted to Biochemical and Biophysical Research Communications.  Co-authors include Tohru and Laura.   A key aspect of this study is the use of primary cell cultures maintained under neural stem cell conditions.  In general, our lab and others are trending away from the use of traditional cell cultures for medulloblastoma, especially when sonic hedgehog signaling might be important.


Again - many congratulations, Sachiko!
 
 
[ Aug 10, 2010:  the manuscript is now available online here. ]
    

News feature on Jackson's Ride the Gorge

We were honored to participate in a news piece tonight by Deb Knapp at KATU in Portland about a sarcoma fundraiser, Jackson's Ride the Gorge.  This event is conducted by the NW Sarcoma Foundation this year and past years in memory of Jackson, a young man who lost his battle with osteosarcoma.  For the online video link, see http://www.katu.com/home/video/99592974.html .  

To register for the Ride, click here. 

Scientific Presentations in Scottsdale and Princeton

It was an exciting week for the Keller laboratory, with three presentation;  1 on rhabdomyosarcoma (Charles) & 1on satellite cells (Tohru) at the FASEB Muscle Satellite and Stem Cell Conference in Carefree (Scottsdale), Arizona, and 1 on rhabdomyosarcoma (Charles) at the Molecular Therapeutics Cancer Research Association Conference at Princeton University.  All three presentations were received well, and what we hope is that more muscle stem cell biologists, and more pharmaceutical industry scientists, will become interested in rhabdomyosarcoma biology and therapy.  In there, somewhere, was a red-eye flight, but it was certainly worth the extra effort.
  
  
[  above right:  FASEB meeting with Michael Kyba (Univ of Minnesota), Charles and Andrew Brack (MGH/Harvard)  ]
[  below right:  CMTRA meeting at Princeton University  ]
  
  

Tohru's FASEB Muscle Stem Cell Talk

Congratulation to Tohru whose work in our lab on "The Role of Rb in Skeletal Muscle Stem Cell Pool Homeostasis" has been selected as platform talk for the upcoming FASEB Muscle Satellite and Stem Cell Conference in Carefree, Arizona.

Welcoming Jen

We would like to welcome Jennifer Alabran as an important staff scientist and lab manager for the Keller lab at OHSU.  Jen received a B.Sc. in Biology from Allegheny College, then went to the National Cancer Institute as a Cancer Research Training Award Fellow in the laboratory of Dr. John Letterio.  When Dr. Letterio's laboratory moved to Case Western Reserve University, Jen enrolled in graduate school and received a M.Sc. in Pathology and Cancer Biology.  From these studies, Jen is first author of the report of a synthetic trierpenoid therapeutic for neuroblastoma.  Most recently Jen has been developing a preclinical cancer model in the T cell biology laboratory of Dr. Mark Jutila.  Jen has a strong commitment to children with cancer in and out of the laboratory, and volunteers annually at camp for children with cancer in Montana.  

Welcoming Monika!

Dr Monika Davare will be joining our laboratory on September 1 as a staff scientist and as our pediatric brain tumor research projects leader.  Monika has strong research portfolio, to be sure.  In the Keller laboratory, she will lead our team investigating factors responsible for medulloblastoma progression and leptomeningeal metastasis.  We look forward to having Monika as a member of our team!

"  I received my PhD from the Molecular and Cellular Pharmacology Program at the University of Wisconsin – Madison. While in Madison, in Johannes Hell’s laboratory, I identified novel signaling complexes associated with CaV1.2 voltage gated calcium channel and demonstrated spatio-temporal regulation of the channel via associated adrenergic signaling complex. We published these data in the Journal of Biological Chemistry and in Science. In our PNAS paper we show the molecular mechanism for calcium channel upregulation that likely contributes to the calcium dysregulation in aging neurons correlated to age related neurodegeneration.

  

As a postdoctoral fellow with Dr. Thomas Soderling (at the Vollum Institute, OHSU), I have characterized the novel signaling complexes associated with calcium/calmodulin regulated kinases, including CaMKK and CaMK1g and identified the role of these kinases during neuronal development, including axonogenesis, activity regulated dendrite/spine formation as well as synaptic plasticity. These data were published as primary and secondary author papers in Journal of Neuroscience, Journal of Biological Chemistry, PNAS and Molecular and Cellular Neuroscience. With my extensive background in neuronal signal transduction, I am now highly motivated to focus research efforts on understanding the histogenesis and dissemination of brain tumors, particularly medulloblastoma and glioma.

  

As such with the Knight Cancer Foundation’s Career Development Award, I am exploring the role of calcium kinase signaling during medulloblastoma migration.   In the coming year, I hope to intensify and focus these efforts, casting a wider net for putative therapeutic targets in Charles Keller’s laboratory. "

    

Introducing Liz

As our laboratory transition from Texas to Portland, we'd like to acknowledge one of the key people who are helping make the process a success.  Elizabeth 'Liz' Perkins is the Administrative Coordinator for the Pediatric Cancer Biology Program and other laboratories within the Pape' Family Pediatric Research Institute.  Liz has extensive professional experience in enterprise-level organizations, as well as volunteerism, special events planning and entrepreneurship.  Liz's experience in managing and organizing executive (board) level activities gives her a special insight into what makes a process successful, as well as how to avoid common pitfalls.  We are grateful that Liz is a part of our team and look forward to growing a highly productive program with her as our founding team member.  

Welcoming Elaine

We are excited to welcome Elaine Huang as operational manager of the Pediatric Preclinical Testing Initiative at OHSU.  Elaine hails from Baton Rouge, Louisiana, and received her B.S. in Microbiology from the University of Michigan.  Elaine then attended graduate school at the University of Pennsylvania where she earned a M.Sc. in Immunology under Dr. Christopher Hunter studying host responses to T. gondii.  Elaine's professional experiences include working in an industry-sponsored GLP/GMP clinical cell and vaccine production facility at U Penn.  Most recently Elaine was a research associate at the Transgenic Mouse Model Shared Resource at OHSU, generating diverse genetically modified mouse models for the researchers using a full spectrum of reproductive technologies.  In her off hours Elaine spends 'too much time' reading and knitting, that is when she’s not running around the various 'woodsy' parts of Oregon.  Elaine will work in concert with Dr. Jinu Abraham, scientific manager of the PPTI, to discover and develop novel new treatments for childhood cancers.    Welcome, Elaine!

Welcoming Audra

Our laboratory welcomes Audra Lee to our team of basic and translational scientists in the Keller lab at OHSU.  Audra earned both B.S. and M.S. degrees in Biology from Ball State University before becoming an important contributing scientist to the laboratory of Dr. Robert Wechsler-Reya, a colleague and one of the rising stars in childhood medulloblastoma research.  In Rob's lab, Audra was first author on an important study on postnatal neural stem cells of the cerebellum published in Nature Neuroscience.  Audra also has vital experience in the biotechnology field having worked at Zen Bio, Inc, in Research Triangle Park, NC.  In her free time, Audra is an aspiring author and enjoys exploring the outdoors.
     In our laboratory, Audra will work to further develop an exciting in ovo system for discovering drugs that inhibit metastasis which has been developed thus far by means of an Innovation Grant the Alex's Lemonade Stand Foundation.  


Welcome, Audra!
    

Welcoming Summer Student, Lauren Peterson

It is our pleasure to welcome Lauren to the lab team.  Lauren will be researching and writing a manuscript on an important aspect of pediatric clinical research.  This is a project for which her undergraduate studies and her social advocacy roles makes her especially qualified:

"I’ve grown up in eastern Washington and am attending Walla Walla University as a Humanities major with a Chemistry minor. I enjoy working with kids, whether it’s teaching swimming lessons or being a camp counselor. As well as working with kids, I enjoy writing and editing, which is why I am very excited to work on this writing project with Dr. Keller this summer.        -- Lauren   "  
    
   

Welcoming Ken

We are pleased to welcome physician-scientist Dr. Ken Kikuchi as a postdoctoral fellow to our laboratory starting July 1.  Ken Received his MD and PhD degrees from Kyoto Prefectural University of Medicine in 1999 and 2008, respectively.  For his PhD, Ken studied under Dr. Hajime Hosoi.  The results of Ken's studies on the effects of the Pax3:Fkhr oncogene on alveolar rhabdomyosarcoma are published in the Biochemical and Biophysical Research Communications.  Ken's long term career goal is to be the principal investigator of an independent academic research laboratory studying rhabdomyosarcoma biology.  Welcome, Ken!

You Can Participate in our Novel Therapeutics Studies !

One would like to think that tangibly better treatments for rhabdomyosarcoma, medulloblastoma and other childhood cancers can be found in a matter of years, instead of tens of years. Finding new treatments starts with research, perhaps even a new research approach to identifying effective new treatments. The Pediatric Preclinical Testing Initiative (at the Pediatric Cancer Biology Program, Pape' Family Pediatric Research Institute, Oregon Health & Science University) focuses on finding molecules in childhood cancers that can be directly turned off or on by drugs so that the tumor stops growing. Behind our novel approach is the use of genetically-engineered mice. Our Pediatric Preclinical Testing Initiative uses mice modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. These special mouse models of childhood cancer can be used to test a treatment to see whether the tumor growth and spread (metastasis) can be reversed. The specific aspect of these mice having normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

 Our program is designed around community participation. Through the Doernbecher Children's Hospital Foundation at OHSU, you can contribute directly to this grass-roots initiative. Donations through small gifts or grants will assist in studying compounds that may be effective in treating such childhood cancers as alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma, or medulloblastoma (the alveolar rhabdomyosarcoma model was featured by Dr. Keller's long time collaborator and former mentor, 2007 Nobel laureate Mario Capecchi, in his Nobel Prize lecture.) For example, a grant of $8500 enabled the PPTI to study a promising multi-kinase inhibitor in mice with alveolar rhabdomyosarcoma.


For additional information regarding supporting this program please contact Ms. Sue Nicol, Doernbecher Children's Hospital Foundation, at nicols(at)ohsu.edu . For additional information on this program, please contact PPTI leader Dr. Charles Keller at keller@ohsu.edu. Results obtained through these studies will be shared with the National Cancer Institute’s Cancer Therapy Evaluation Program, as well as the Children’s Oncology Group, which designs clinical trials for childhood cancer.

Acknowledging the Amazing Team at GCCRI

As our laboratory moves officially from San Antonio to OHSU in Portland next week, it's important to acknowledge the incredibly talented group we've been able to work with at GCCRI in San Antonio.  
    

In the time since our lab started in 2005, we've published over 2 dozen papers with funding in the form of R01(s), NIH S10 grants and other competitive awards.  All this was possible through the hard work and intellectual contributions of postdoctoral fellows including:


- Eri Taniguchi (who went on to a second fellowship at MGH/Harvard and is now at Cincinnati Children's Hospital), 
- Koichi Nishijo (who is now Clinical Leader in Oncology Therapeutic Development, Bayer Japan), 
- Sachiko Ohshima (who has gone on to a second fellowship with Dr. Marina Emborg, Univ. of Wisconsin, Madison), 
- Tohru Hosoyama (who has gone on to a second fellowship with Dr. Masatoshi Suzuki, Univ. of Wisconsin, Madison), 
- Min Jung Cho (who is now faculty in the Dept of Pediatrics, Busan National University Hospital, Korea), 
- Anu Soundararajan (who has gone on to a second fellowship with Dr. Peter Fox at Research Imaging Institute, UTHSCSA), 
- Aoife Kilcoyne (who is a Radiology Resident in Dublin, Ireland),  and 
- Jinu Abraham (who will be taking an important leadership role with the PPTI in our lab at OHSU).  


We've also had the good fortune to have diligent, kind-hearted and highly effective scientific staff, including the tireless Laura Nelon, Xiaolan Yi, Beverly Schaffer and Sheila Hampton.  Laura, Xiaolan and Sheila made the move possible, and I personally can't thank them enough.  In fact, there are almost no words that can adequately express our appreciation.  The single most productive person, at least by authorship count, would be Suresh Prajapati, who managed our Small Animal Imaging Resource Facility with incredible efficiency and professionalism. 


We graduated four graduate students, Patrick "P.J." Hawkes, Lisa Nevell, Corrine Chua, and the award-winning Aislynn Samano.  Aislynn was particularly resilient in finding a way to rate therapies for medulloblastoma using our mouse models.  And of course, Lisa is now a postdoctoral fellow with Nobel laureate, Mario Capecchi.  We've had many other part time and Summer students in our lab that we've highlighted previously (including Mandy McCleish, Jerry Chang, Hunter Weibush, Steven McCarthy and Andrea Rodriguez), but it's important to acknowledge the incredible Courtney Kubicek, a nursing student who began each schoolday at 6am by examinations... of our mice!  She will surely be an outstanding nurse anesthetist one day soon.  Medical student Imran Aslam deserves special recognition, too, for working with Tohru to turn an AMA medical student seed grant into an important part of an R01 application that scored 25 (7th percentile). 


The staff at GCCRI deserve our deep thanks, also.  They include our fearless and sage Administrator, Bill Chessher (as a former hospital administrator, rodeo man, heavy equipment operator and poultry farmer, Bill's memoirs should be rather interesting), financial and information technology head Tony Mendicino (who knew both could be done by the same person, and so effectively!), Danette Besancon (the ultimate can-do person), Richard McDougle (to whom all PI's must account), the talented graphics artist David Rodriguez, helpful grantsperson Lucy Hernandez, talented histologist Michelle Brady, flow cytometry aficionado Jenny Rebeles, the gifted network systems engineer Barron Blackman, the sleepless network support person Tony Dennie, as well as the undeniable and very loved facility manager Tracy Byrd and Irma Gonzalez, who we couldn't have done without!  Our heart goes out to Frances 'Fran' Melton, who performed the impossible with our Oncomouse-related MTA's, and colleague Chris Burke, who managed our busy and complex IP portfolio without ever losing her sense of humor.  Gaye, Joe, Richard and Teresa in Purchasing are deeply valued also.  


What can be said of our fearless founding leader, Dr. Sharon Murphy?  Although she's at the Institute of Medicine now, her insights into team building and driving biological problems cannot be surpassed, and we appreciate the opportunity to continue learning from her wisdom.  Our work, too, couldn't have been accomplished without the support of Debbie Morrill and Kim Warshauer. Leslea Sarro and Tammy Linn in lab animal resources literally kept our lab's heart beating. 


Finally, we'd like to thank the Foundations that have supported our work, including the Scott Carter Foundation, Alex's Lemonade Stand Foundation, the National Brain Tumor Society, the Sarcoma Foundation of America, the Amschwand Sarcoma Cancer Foundation, the Rally Foundation and the Joanna McAfee Childhood Cancer Foundation.  Their support has allowed us to create the Pediatric Preclinical Testing Initiative and to pursue high risk, high reward projects that have gone on to successful R01's.  
   
Charles & Team
  

Rhabdomyosarcoma Paper accepted to MCT

Congratulations to co-first authors, Bev Schaffer (Keller lab) and Marcia Grayson (Infante lab) whose manuscript, "Immune Competency of a Hairless Strain for Improved Preclinical Studies in Genetically-Engineered Mice" was accepted today to Molecular Cancer Therapeutics, an AACR Journal.  This study describes a way to improve genetically-engineered mouse models of cancer (particularly rhabdomyosarcoma) by making them fur-free.  Other co-authors include Keller lab current and past members, Laura Nelon, Suresh Prajapati, Joy Wortham, Courtney Kubicek, Mandy McCleish, Michelle Brady and Tohru Hosoyama, as well as collaborators Tony Infante (UTHSCSA Pediatrics & Immunology), Inkyung Jung and Joel Michalek (UTHSCSA Biostatistics), Leslea Sarro and Marti Hanes (UTHSCSA Lab Animal Resources), Brian Rubin (Cleveland Clinic) and Charlie Clifford (Charles River Laboratories).  
                                     
    
[ Update! 7/23/10... exciting news, this paper will be featured as the Cover Article  ] 

R01 grant receives great score (now hiring!)

We are excited that our multiple-PI NIH R01 research grant in collaboration with Dr. Denis Guttridge at OSU has received a very favorable priority score, putting it in the top 7% of grants being reviewed this past cycle.  This grant application addresses the role of NFkB in the childhood muscle cancer.  The preliminary data for this application would not have been possible without the hard work and intellectual contributions of Keller lab postdoctoral fellows, Drs. Sachiko Ohshima and Tohru Hosoyama, as well as key experiments designed and implemented by medical student M. Imran Aslam, who was funded by an AMA Medical Student Research Seed Grant.  


  Naturally, of course, we will be looking for an additional postdoctoral fellow for this project.  Please see our ad in Naturejobs, which is also below:


Postdoctoral Research Fellowship for Signaling in Muscle Stem Cells and Rhabdomyosarcoma.    This mentored position in the Keller laboratory will empower the candidate to create and analyze complex conditional genetic mouse models of pediatric cancers for the purpose of developing novel molecular therapies. The primary goal for this position is to investigate the role of growth factor and cytokine signaling in the childhood muscle cancer, alveolar rhabdomyosarcoma.  
  
Qualifications Required:    MD and/or PhD, preferably with 3-4 years experience in Biochemistry; molecular biology; animal models and animal surgery; small animal imaging; cancer biology.
  
How to Apply:    Please send cover letter and CV with 3 references to Dr. Charles Keller, at keller@ohsu.edu