OHSU

Graduate Studies Faculty

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Leslie L. Muldoon, Ph.D.

Associate Professor
Admin Unit: Blood Brain Barrier and Neuro-Oncology Program
Phone: 503-494-5626
Lab Phone: 503-494-7179
Fax: 503-494-5627
Office: MacHall 5182
Mail Code: L603
Programs:
Cell & Developmental Biology
Neuroscience Graduate Program
Program in Molecular & Cellular Biosciences
Neurology
Research Interests:
brain tumors cancer therapeutics animal models blood-brain barrier magnetic resonance imaging » Click here for more about Dr. Muldoon's research
Preceptor Rotations
Dr. Muldoon has not indicated availability for preceptor rotations at this time.
Faculty Mentorship
Dr. Muldoon has not indicated availability as a mentor at this time.
Profile
Cancers in the brain are difficult to treat because of neurotoxicity, tumor resistance, and minimal delivery of potential therapies across the blood-brain barrier (BBB). The OHSU BBB program conducts basic science, preclinical, and clinical studies of new approaches to delivery, efficacy, and imaging in primary and metastatic brain tumors. I direct the preclinical and basic science research projects in the  Blood-Brain Barrier Program, under the direction of Dr. Edward A. Neuwelt.  I have three general areas of research concentration:

Novel therapies in brain tumor models. We evaluate brain tumor growth, imaging characteristics and response to therapies in rat tumor models including primary brain tumors such as glioma or medulloblastoma, and xenograft and hematogenous lung, melanoma, and breast cancer brain metastasis models. In these animal models we test mechanisms to cross the blood-brain barrier, as well as combination chemotherapy, radiotherapy, and immunotherapy treatment approaches. Our current work centers on modulating the activity of integrin cell surface adhesion molecules. We have demonstrated that blocking alpha-V integrins decreases breast cancer brain metastasis and improves survival. Blocking
alpha-V integrins also alters tumor vascular permeability in rat brain tumors, which may enhance the delivery and efficacy of therapeutics.

Imaging of brain tumors and neurological lesions. We study new magnetic resonance imaging agents and modalities to monitor brain tumor growth and anti-tumor efficacy. We are working with new superparamagnetic iron oxide nanoparticle MR contrast agents, such as ferumoxytol (AMag Pharmaceuticals). Ferumoxytol acts as blood-pool agent in the short term (30 minutes) so can be used for dynamic MRI measurements of tumor vascular permeability and blood volume. Additionally, the nanoparticles have a long plasma half-life coupled with uptake by phagocytic cells. They provide imaging of inflammatory components of brain tumors by a slow leak into the tumor and brain around tumor and uptake by reactive cells in and around the tumor.
           
Chemoprotection. Thiol chemoprotective agents can be used to reduce the toxic side effects of chemotherapy such as ototoxicity, mucositis, nephrotoxicity, and bone marrow toxicity. We are testing whether chemoprotectants may be used to decrease dose reductions secondary to chemotherapy side effects or by allowing dose escalation. Current studies are directed at determining the mechanisms of thiol chemoprotection so that we can more specifically target normal tissues rather than tumor cells.

Background

Dr. Muldoon is an Associate Professor in the Department of Neurology, with a joint appointment in the Department of Cell and Developmental Biology.  She has been in charge of the BBB Program Preclinical laboratory since 1990. Dr. Muldoon directs all preclinical aspects of the program, including experimental protocol development, supervision of technicians and Research Fellows, and writing grant proposals and scientific articles.

Research Interests

Dr. Muldoon has extensive background in tumor and cell biology, magnetic resonance imaging, and histological and immunological methods for assessing neurotoxicity and tumor volumetrics.  She has played a central role in the analysis of chemoprotective agents against chemotherapy toxicity, and the development and imaging of brain tumor models.

Selected Publications

Wu YJ, Muldoon LL, Gahramanov S, Kraemer DF, Marshall DJ, Neuwelt EA. Targeting αv integrins decreased metastasis and increased survival in a nude rat breast cancer brain metastasis model. In press, J Neuro-Oncology, 2012.


Gahramanov S, Muldoon LL, Li X, Neuwelt EA. Improved perfusion MRI using ferumoxytol of intracerebral tumor blood volume and antiangiogenic therapy efficacy in a rat model. Radiology. 2011 Dec;261(3):796-804. Epub 2011 Sep 21. PMID: 2194050

Muldoon LL, Lewin SJ, Dosa E, Kraemer DF, Pagel MA, Doolittle ND, Neuwelt EA. Imaging and therapy with rituximab anti-CD20 immunotherapy in an animal model of central nervous system lymphoma. Clin Cancer Res. 17(8):2207-2215, 2011. PMID: 21385922

Muldoon LL, Gahramanov S, Li X, Marshall DJ, Kraemer DF, Neuwelt EA. Dynamic magnetic resonance imaging assessment of vascular targeting agent effects in rat intracerebral tumor models. Neuro Oncol 13(1): 51-60, 2011. PMID: 21123368

Education

Dr. Muldoon obtained a B.S. in Chemistry (1982) and a Ph.D. in Pharmacological and Physiological Sciences (1986) from the University of Chicago, and completed a Post-Doctoral Fellowship in the OHSU Department of Cell Biology and Anatomy in 1990.

Links

Neuro-Oncology Blood-Brain Barrier Program