Laboratory of Jessica Kandel, MD
Principal Investigator
Jessica Kandel, MD
- Surgery Residency: Massachusetts General Hospital
- Research Fellowship: Boston Children’s Hospital (Dr. Judah Folkman’s laboratory)
- Pediatric Surgical Fellowship: Johns Hopkins Hospital
Background for Research focus:
New blood vessel growth, or angiogenesis, is requisite for the growth and metastasis of solid tumors. Blockade of vascular endothelial growth factor (VEGF), a key promoter of angiogenesis, has recently been validated as a therapeutic strategy in clinical trials. However, it has also been demonstrated that tumors can recur after an initial response to VEGF blockade. Preliminary work implicates mechanisms that increase vascular stability, such as enhanced recruitment of vascular smooth muscle to tumor vessels. However, the molecular determinants of this response to sustained anti-angiogenesis have not been defined.
Main Focus of the Laboratory:
Using orthotopic metastasizing models of pediatric neuroblastoma and Wilms tumor, we investigate tumor and vascular responses to VEGF blockade. We hypothesize that sustained VEGF blockade will result in (1) a program of vascular recovery, mediated by alterations in expression of angiogenic growth factors, matrix glycoproteins, and anti-apoptotic signaling pathways in endothelium and (2) alterations in tumor expression profile, leading to increased support of vasculature and decreased apoptosis/increased proliferation of tumor cells.
Current Projects:
- Functions of angiopoietin-1 in vascular regression and recovery in Wilms tumor
- Vascular phenotype of PDGFB-deficient tumors
- Effects of blocking VEGF translation in tumors
- Role of Id2 and neurotrophins in regulating angiogenesis in neuroblastoma
- Role of COX2 in Wilms tumor angiogenesis and tumorigenesis
Recent Publications:
Huang J, Frischer JS, New T, Kim ES, Serur A, Lee A, Kadenhe-Chiwishe A, Pollyea DA, Yokoi A, Holash J, Yancopoulos GD, Kandel JJ, Yamashiro DJ. TNP-470 promotes initial vascular sprouting in xenograft tumors. Mol Cancer Ther. 2004 Mar;3(3):335-43.
Frischer JS, Huang J, Serur A, Kadenhe A, Yamashiro DJ, Kandel JJ. Biomolecular markers and involution of hemangiomas. J Pediatr Surg. 2004 Mar;39(3):400-4.
Davidoff AM, Kandel JJ. Antiangiogenic therapy for the treatment of pediatric solid malignancies. Semin Pediatr Surg. 2004 Feb;13(1):53-60.
Huang J, Soffer SZ, Kim ES, McCrudden KW, Huang J, New T, Manley CA, Middlesworth W, O'Toole K, Yamashiro DJ, Kandel JJ. Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis. Mol Cancer Res. 2004 Jan;2(1):36-42.
Yokoi A, McCrudden KW, Huang J, Kim ES, Soffer SZ, Frischer JS, Serur A, New T, Yuan J, Mansukhani M, O'toole K, Yamashiro DJ, Kandel JJ. Human epidermal growth factor receptor signaling contributes to tumor growth via angiogenesis in her2/neu-expressing experimental Wilms' tumor. J Pediatr Surg. 2003 Nov;38(11):1569-73.
Kaicker S, McCrudden KW, Beck L, New T, Huang J, Frischer JS, Serur A, Kadenhe-Chiweshe A, Yokoi A, Kandel JJ, Yamashiro DJ. Thalidomide is anti-angiogenic in a xenograft model of neuroblastoma. Int J Oncol. 2003 Dec;23(6):1651-5.
Yokoi A, McCrudden KW, Huang J, Kim ES, Soffer SZ, Frischer JS, Serur A, New T, Yuan J, Mansukhani M, O'Toole K, Yamashiro DJ, Kandel JJ. Blockade of her2/neu decreases VEGF expression but does not alter HIF-1 distribution in experimental Wilms tumor. Oncol Rep. 2003 Sep-Oct;10(5):1271-4.
Huang J, Frischer JS, Serur A, Kadenhe A, Yokoi A, McCrudden KW, New T, O'Toole K, Zabski S, Rudge JS, Holash J, Yancopoulos GD, Yamashiro DJ, Kandel JJ. Regression of established tumors and metastases by potent vascular endothelial growth factor blockade. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7785-90.
Glade-Bender J, Kandel JJ, Yamashiro DJ. VEGF blocking therapy in the treatment of cancer. Expert Opin Biol Ther. 2003 Apr;3(2):263-76.
Kim ES, Serur A, Huang J, Manley CA, McCrudden KW, Frischer JS, Soffer SZ, Ring L, New T, Zabski S, Rudge JS, Holash J, Yancopoulos GD, Kandel JJ, Yamashiro DJ. Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma. Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11399-404.
Recent (last 5 years) Surgery Residents (Columbia and outside):
Jae-O Bae (job14@columbia.edu)
Angela Kadenhe-Chiweshe (avk2102@columbia.edu)
Jason Frischer (jason.frischer@mssm.edu)
Kim McCrudden (kwm4@columbia.edu)
Eugene Kim (peds surgery fellow at Cinncinnati Children’s, don’t have his email)
Sam Soffer (soff3@aol.com)
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