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Biochemical Pathology Section

David D. Roberts, Ph.D.

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Primary Research Areas

Areas of expertise

Tumor vascular biology

Tumor immunology

Signal transduction

Extracellular matrix biology

Redox and radiation biology

Glycobiology

Stem cell biology

Candidia pathogenesis

Technologies / approaches / methodologies

Cell biology: angiogenesis, autophagy, cell motility, stem cell

reprogramming, radiation responses

Biochemistry: cell surface receptor signaling, metabolomics

Molecular biology

Transgenic mice

Mouse tumor models including treatment and imaging

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Targeting CD47 in tumors and their microenvironment

CD47 blockade increases cell

survival via:

Nitric oxide signaling

Autophagy

c-Myc and other stem cell factors

Metabolic reprogramming

Increased repair of DNA damage

Genotoxic stress

Tumor

cells

Genotoxic

stress

Macrophages

Stroma:

CD47 blockade increases tumor

cell death via: Decreasing protective

autophagy

Resistance to c-Myc regulation

Decreased resistance to innate

and adaptive immunity

T cells

Tumor:

Tumor

vasculature

Irrad.

Irrad.+

CD47M

Time after radiation (days)

Meantumorvolume

(cm3)

0 6 12 18 24 30

0

.3

.6

.9

1.2

1.5 TumorTumor+Irrad.

Tumor+Irrad+CD47MTumor+CD47M

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Research Implications

How does your research fit in LP and the broader context? We are developing new insights into the pathogenesis

of cancer that can be applied for improving diagnostic

and prognostic evaluation (e.g. CD47 expression)

We are developing new treatment modalities forimproving the responses of cancer patients to

radiotherapy and chemotherapy

How does your research translate into potential clinical

applications? We are using animal models to evaluate and optimize

novel therapeutics targeting CD47 that can improve

patient survival and increase curative responses

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Future Directions

Where do you see your research going in the next 5-10 years?Preclinical and clinical development of antisense and

small molecule CD47 inhibitors

Applications to cancer radiotherapy, chemotherapy, and

immunotherapyBasic research addressing CD47 signaling to regulate

angiogenesis, autophagy, immunity, stem cell

reprogramming, and cancer stem cells

What are the current challenges & obstacles?

Preclinical pharmacology to support an IND for translation

of CD47-based therapeutics to clinical trials

Establishing clinical collaborations to initiate clinical trials

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Collaborators partial list

Laboratory of Pathology

CCR

NIH

Extramural

Maria Merino molecular markers and metabolism in familial kidney cancers

David Levens & Eric Batchelor cMyc regulation by thrombospondin-1 and CD47

David Wink, RBB (radioprotection and radiosensitization by modulating CD47)

Marc Nicklaus, Chemical Biology Laboratory (design of small molecule CD47 inhibitors)Jay Berzovsky, Vaccine Branch (regulation of adaptive tumor immunity by CD47)

Chengyu Liu, iPSC and Genome Engineering Core, NHLBI (stem cells)

Abdel Elkahloun, Cancer Genetics Branch, NHGRI (stem cells and cancer stem cells)

Satya Singh, Laboratory of Molecular Immunology, NIAID (immune regulation)

Michail Lionakis, NIAID (Candida pathogenesis)Martin Lizak, NINDS (MRI imaging)

Jeff Isenberg, University of Pittsburgh (CD47 signaling and animal models)

Maria Tsokos, Harvard (animal model pathology)

Chris Kevil, LSU (hydrogen sulfide signaling)Ken Nickerson, University of Nebraska (Candida pathogenesis)