Dorothy Sipkins

Positions:

Associate Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Associate Research Professor in Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Duke Regeneration Center

Regeneration Next Initiative
School of Medicine

Education:

M.D. 1999

Stanford University, School of Medicine

Ph.D. 1999

Stanford University, School of Medicine

Internship and Residency, Internal Medicine

Massachusetts General Hospital

Hematology-Oncology Fellowship, Hematology Oncology

Dana-Farber Cancer Institute

Grants:

Targeting sphingosine kinase 2 for the treatment of multiple myeloma

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Defining the Rules of Breast Cancer Cell Traffic Through Bone

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Targeting Dormant Breast Cancer Micrometastases to Prevent Disease Relapse

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
American Cancer Society, Inc.
Role
Principal Investigator
Start Date
End Date

Role of Osteopontin in Induction of Leukemia Dormancy in the Bone Marrow

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
American Cancer Society, Inc.
Role
Principal Investigator
Start Date
End Date

Studying the Effects of Combined E-Selectin/CXCR4 Inhibition on Breast Cancer Cell Metastasis, Growth and Immune Regulation

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
GlycoMimetics, Inc
Role
Principal Investigator
Start Date
End Date

Publications:

Leukaemia: a model metastatic disease.

In contrast to solid cancers, which often require genetic modifications and complex cellular reprogramming for effective metastatic dissemination, leukaemic cells uniquely possess the innate ability for migration and invasion. Dedifferentiated, malignant leukocytes retain the benign leukocytes' capacity for cell motility and survival in the circulation, while acquiring the potential for rapid and uncontrolled cell division. For these reasons, leukaemias, although not traditionally considered as metastatic diseases, are in fact models of highly efficient metastatic spread. Accordingly, they are often aggressive and challenging diseases to treat. In this Perspective, we discuss the key molecular processes that facilitate metastasis in a variety of leukaemic subtypes, the clinical significance of leukaemic invasion into specific tissues and the current pipeline of treatments targeting leukaemia metastasis.
Authors
Whiteley, AE; Price, TT; Cantelli, G; Sipkins, DA
MLA Citation
Whiteley, Andrew E., et al. “Leukaemia: a model metastatic disease.Nat Rev Cancer, vol. 21, no. 7, July 2021, pp. 461–75. Pubmed, doi:10.1038/s41568-021-00355-z.
URI
https://scholars.duke.edu/individual/pub1482284
PMID
33953370
Source
pubmed
Published In
Nat Rev Cancer
Volume
21
Published Date
Start Page
461
End Page
475
DOI
10.1038/s41568-021-00355-z

Rendering the leukemia cell susceptible to attack.

Authors
MLA Citation
Sipkins, Dorothy A. “Rendering the leukemia cell susceptible to attack.N Engl J Med, vol. 361, no. 13, Sept. 2009, pp. 1307–09. Pubmed, doi:10.1056/NEJMcibr0904291.
URI
https://scholars.duke.edu/individual/pub1025910
PMID
19776414
Source
pubmed
Published In
The New England Journal of Medicine
Volume
361
Published Date
Start Page
1307
End Page
1309
DOI
10.1056/NEJMcibr0904291

Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells.

The host tissue microenvironment influences malignant cell proliferation and metastasis, but little is known about how tumor-induced changes in the microenvironment affect benign cellular ecosystems. Applying dynamic in vivo imaging to a mouse model, we show that leukemic cell growth disrupts normal hematopoietic progenitor cell (HPC) bone marrow niches and creates abnormal microenvironments that sequester transplanted human CD34+ (HPC-enriched) cells. CD34+ cells in leukemic mice declined in number over time and failed to mobilize into the peripheral circulation in response to cytokine stimulation. Neutralization of stem cell factor (SCF) secreted by leukemic cells inhibited CD34+ cell migration into malignant niches, normalized CD34+ cell numbers, and restored CD34+ cell mobilization in leukemic mice. These data suggest that the tumor microenvironment causes HPC dysfunction by usurping normal HPC niches and that therapeutic inhibition of HPC interaction with tumor niches may help maintain normal progenitor cell function in the setting of malignancy.
Authors
Colmone, A; Amorim, M; Pontier, AL; Wang, S; Jablonski, E; Sipkins, DA
MLA Citation
Colmone, Angela, et al. “Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells.Science, vol. 322, no. 5909, Dec. 2008, pp. 1861–65. Pubmed, doi:10.1126/science.1164390.
URI
https://scholars.duke.edu/individual/pub1025902
PMID
19095944
Source
pubmed
Published In
Science
Volume
322
Published Date
Start Page
1861
End Page
1865
DOI
10.1126/science.1164390

MALIGNANT GROWTH IN THE BONE MARROW CREATES ABNORMAL HEMATOPOIETIC PROGENITOR CELL NICHES

Authors
Colmone, A; Amorim, M; Pontier, A; Wang, S; Jablonski, E; Sipkins, DA
MLA Citation
Colmone, Angela, et al. “MALIGNANT GROWTH IN THE BONE MARROW CREATES ABNORMAL HEMATOPOIETIC PROGENITOR CELL NICHES.” Anticancer Research, vol. 28, no. 5C, INT INST ANTICANCER RESEARCH, Sept. 2008, pp. 3555–3555.
URI
https://scholars.duke.edu/individual/pub1025907
Source
wos
Published In
Anticancer Research
Volume
28
Published Date
Start Page
3555
End Page
3555

Leukaemia hijacks a neural mechanism to invade the central nervous system.

Acute lymphoblastic leukaemia (ALL) has a marked propensity to metastasize to the central nervous system (CNS). In contrast to brain metastases from solid tumours, metastases of ALL seldom involve the parenchyma but are isolated to the leptomeninges, which is an infrequent site for carcinomatous invasion. Although metastasis to the CNS occurs across all subtypes of ALL, a unifying mechanism for invasion has not yet been determined. Here we show that ALL cells in the circulation are unable to breach the blood-brain barrier in mice; instead, they migrate into the CNS along vessels that pass directly between vertebral or calvarial bone marrow and the subarachnoid space. The basement membrane of these bridging vessels is enriched in laminin, which is known to coordinate pathfinding of neuronal progenitor cells in the CNS. The laminin receptor α6 integrin is expressed in most cases of ALL. We found that α6 integrin-laminin interactions mediated the migration of ALL cells towards the cerebrospinal fluid in vitro. Mice with ALL xenografts were treated with either a PI3Kδ inhibitor, which decreased α6 integrin expression on ALL cells, or specific α6 integrin-neutralizing antibodies and showed significant reductions in ALL transit along bridging vessels, blast counts in the cerebrospinal fluid and CNS disease symptoms despite minimally decreased bone marrow disease burden. Our data suggest that α6 integrin expression, which is common in ALL, allows cells to use neural migratory pathways to invade the CNS.
Authors
Yao, H; Price, TT; Cantelli, G; Ngo, B; Warner, MJ; Olivere, L; Ridge, SM; Jablonski, EM; Therrien, J; Tannheimer, S; McCall, CM; Chenn, A; Sipkins, DA
MLA Citation
Yao, Hisayuki, et al. “Leukaemia hijacks a neural mechanism to invade the central nervous system.Nature, vol. 560, no. 7716, Aug. 2018, pp. 55–60. Pubmed, doi:10.1038/s41586-018-0342-5.
URI
https://scholars.duke.edu/individual/pub1335790
PMID
30022166
Source
pubmed
Published In
Nature
Volume
560
Published Date
Start Page
55
End Page
60
DOI
10.1038/s41586-018-0342-5