V. Drozdoff | Cold Spring Harbor Laboratory (original) (raw)

Papers by V. Drozdoff

Cold Spring Harbor perspectives in medicine

Appropriate negotiation and drafting of license agreements are critical to successfully establish... more Appropriate negotiation and drafting of license agreements are critical to successfully establishing and managing the expansive and complex relationships that are becoming more common between industry and universities. More often than not, the resulting licensing agreements become quite lengthy and complex, and the key principles become difficult to discern among all the details. This summary provides a short, nonexhaustive introduction to some of the essential components of these licenses with the intent of providing the non-licensing professional a better appreciation of some of the key commercial and legal terms from both an academic and company perspective, keeping in mind some of the considerations that particularly apply to biotechnology deals.

Oncogene research, 1988

Mouse C3H10T1/2 cells were co-transfected with a plasmid containing the KiSV DNA and a plasmid ca... more Mouse C3H10T1/2 cells were co-transfected with a plasmid containing the KiSV DNA and a plasmid carrying sequences coding for resistance to mycophenolic acid. Only 30% of the transfected colonies had a transformed phenotype, i.e. highly refractile rounded cells. The remaining colonies had varied morphologies with flat or slightly elongated cells. Analysis of p21 ras protein indicated that higher levels of the protein were expressed in cells with the more transformed phenotype. Tumors formed by a poorly tumorigenic clone were found to have undergone in vivo amplification of the transfected KiSV sequence. Transformed variants of this clone were also isolated in vitro. Treatment with 5-azacytidine resulted in an increase of about 10 fold in the formation of transformed variants. All transformed cells isolated, either spontaneous or 5-azacytidine induced, were tumorigenic in nude mice. The neoplastic conversion of these cells was accompanied by amplification of the transfected K-ras sequ...

Proceedings of the National Academy of Sciences, 1994

Decapentaplegic Vg-related protein 6 (DVR-6 or bone morphogenetic protein BMP-6) is a member of t... more Decapentaplegic Vg-related protein 6 (DVR-6 or bone morphogenetic protein BMP-6) is a member of the DVR subgroup of the transforming growth factor beta superfamily, a large group of multifunctional signaling polypeptides that are expressed as secreted disulfide-bonded dimers proteolytically cleaved from larger precursors. The predominant expression of DVR-6 in the differentiating postmitotic layers of stratified squamous epithelia strongly suggests a role for DVR-6 in regulation of epithelial differentiation. In primary mouse keratinocytes induced to differentiate by suspension culture in methylcellulose, new expression of DVR-6 mRNA and protein was detected within 8 h among a majority of the suspended cells, which preceded the induction of expression of the suprabasal keratins K1 and K10. To test the hypothesis that DVR-6 is a keratinocyte growth regulatory factor, a retroviral expression vector expressing human DVR-6 was used to infect attached cultures of undifferentiated basal c...

Proceedings of the National Academy of Sciences, 1986

The c-myc oncogene has been implicated in deregulation of cell growth in neoplastic cells and res... more The c-myc oncogene has been implicated in deregulation of cell growth in neoplastic cells and response to "competence-inducing" growth factors in normal cells. In the latter case, expression of c-myc has been shown to be associated with the transition from the G0 to the G1 phase of the cell cycle induced by platelet-derived growth factor (PDGF). In the work reported here, we have introduced the c-myc coding region, in a retroviral vector, into mouse and rat cells. We show that under conditions of anchorage-independent growth, constitutive c-myc expression increases the response of rodent cells to PDGF, as well as to other growth factors of both the competence-inducing and "progression" classes. These effects of the myc product are observed whether or not an exogenous ras gene has also been introduced into the same cells. Possible models for the influence of myc on growth responses are discussed.

Proceedings of the National Academy of Sciences, 1987

C3H/10T1/2 cells were infected with a retroviral vector expressing a mouse c-myc oncogene and a d... more C3H/10T1/2 cells were infected with a retroviral vector expressing a mouse c-myc oncogene and a drug-selection marker. The resulting cells, morphologically indistinguishable from C3H/10T1/2, displayed a greatly enhanced sensitivity to neoplastic transformation by ionizing radiation or by a chemical carcinogen. Constitutive expression of myc therefore appears to synergize with an initial carcinogenic event, providing a function analogous to a subsequent event that apparently is required for the neoplastic transformation of these cells. This cell system should prove useful in exploring early stages in radiation-induced transformation.

Annals of the New York Academy of Sciences, 1987

Epidemiological surveys of occurrence of human neoplastic disease as well as in‐vitro and in‐vivo... more Epidemiological surveys of occurrence of human neoplastic disease as well as in‐vitro and in‐vivo experimental models indicate that tumorigenesis is a multistep process involving independent genetic events.1‐3 In particular, studies with retroviruses and cloned oncogenes demonstrate that cooperation between oncogenes is required for full transformation of primary embryo cells in culture.4–8Differences in response to growth factors can be observed between normal cells, which are capable of limited replication and are poorly transformable, and established cell lines, which can be more easily transformed by transfer of cloned oncogenes or exposure to carcinogens.9 Recent reports have provided evidence for effects of some oncogenes at specific points along biochemical pathways that regulate mitosis.10–13 For example, altered expression of the myc gene has been implicated in stimulation of cell growth in response to competence‐inducing growth factors in normal cells and deregulation of c...

Journal of the American Society of Nephrology, 1999

Developmental assembly of the renal microvasculature requires spatially and temporally coordinate... more Developmental assembly of the renal microvasculature requires spatially and temporally coordinated migration, assembly, differentiation, and maturation of endothelial cells in the context of adjacent epithelial and mesangial cells. In this study, endothelial expression and distribution of the receptor tyrosine phosphatase ECRTP/DEP-1 were evaluated during and after developmental assembly of the renal microvasculature. Monoclonal antibodies against ECRTP/DEP-1 ectodomain epitopes localize its expression to membrane surfaces of endothelial cells in glomerular, peritubular capillary, and arterial renal sites of mature human and murine kidney. During kidney development, ECRTP/DEP-1 immunostaining is evident on a subpopulation of metanephric mesenchymal cells and on putative progenitors of glomerular capillary endothelial cells early in their recruitment to developing glomeruli. ECRTP/DEP-1 is prominently displayed on luminal membrane surfaces with punctate accumulations at inter-endothelial contacts that overlap with vascular endothelial-cadherin staining. ECRTP/DEP-1 is recruited to inter-endothelial contacts in confluent cultured human renal and dermal microvascular endothelial cells, yet experimental dissociation of vascular endothelial-cadherin from endothelial junctional complexes fails to redistribute ECRTP/DEP-1. These findings indicate that ECRTP/DEP-1 is expressed in anticipation of glomerular capillary endothelial recruitment during development, and suggest that ECRTP/DEP-1 ectodomain interacts with endothelial surface ligands that are engaged by cell-cell contact. Development of renal glomerular capillaries is anatomically segregated and temporally staged in a multistep process that involves recruitment of endothelial progenitors from adjacent mesenchyme, assembly of an arborized branching network, and maturation and specialization of endothelial cells adjacent to mesangial and visceral epithelial cells (1,2). Endothelial cell surface receptors are important mediators of this assembly process, because they interact with ligands secreted by adjacent cells, with extracellular matrix, and with surface molecules on cells they contact. Among growth factors, vascular endothelial growth factor (VEGF) is an important participant. VEGF is induced in S stage glomerular epithelial cells, and endothelial progenitors that are recruited to glomerular capillaries from the adjacent metanephric mesenchyme express the VEGF receptor flk-1 (3,4). Neutralizing VEGF antibodies interrupt postnatal murine glomerular capillary development (5). Homozygous deletion of either platelet-derived growth factor-␤ (PDGF-␤) receptor or PDGF B/c-sis genes in mice causes defective recruitment of

The Journal of biological chemistry, Jan 15, 1991

Platelet-derived growth factor (PDGF) and its receptor exist in multiple forms. PDGF exists in th... more Platelet-derived growth factor (PDGF) and its receptor exist in multiple forms. PDGF exists in three dimeric combinations of A and B subunit chains, which are the products of separate genes. The PDGF receptor is similarly encoded by genes for two distinct receptor proteins, alpha and beta. A recent model proposed PDGF binding involves the association of the two receptor proteins into three possible dimeric forms. An essential prediction of that model is that PDGF alpha-receptors are required for cells to bind and respond to the heterodimeric AB isoform of PDGF. In contrast, we found both binding and functional response to PDGF-AB was retained in Balb/c-3T3 cells after PDGF alpha-receptors had been down-regulated by PDGF-AA pretreatment. The observation that PDGF-AB could still elicit these responses suggests that at 37 degrees C, PDGF-AB may bind directly to beta-receptors in either monomeric or dimeric forms and that initial receptor activation may occur independently of the format...

The Journal of Cell Biology, 1993

In the epidermis, one of the earliest characterized events in keratinocyte differentiation is the... more In the epidermis, one of the earliest characterized events in keratinocyte differentiation is the coordinate induction of a pair of keratins specifically expressed in suprabasal cells, keratin 1 (K1) and keratin 10 (K10). Both in vivo and in vitro, extracellular calcium is necessary for several biochemical and structural changes during keratinocyte differentiation. However, it has been unclear if calcium serves as a differentiation signal in keratinocytes. In these studies, expression of suprabasal keratin mRNA and protein is used to test whether the initial differentiation of primary mouse keratinocytes in vitro is dependent on changes in the concentration of extracellular calcium. K1 mRNA was expressed at low levels in cultures of keratinocytes growing on plastic in 0.05 mM calcium but in attached cells was not further induced by increases in the concentration of extracellular calcium. Suspension of the keratinocytes into semi-solid medium induced a rapid and substantial increase in both expression of K1 mRNA and in the percentage of cells expressing suprabasal keratin proteins. The induction was unaffected by the concentration of calcium in the semi-solid medium and could not be enhanced by exposing attached cells to higher calcium before suspension. The induction of K1 mRNA could be inhibited by exposure of the keratinocytes to either EGF or fibronectin. These results suggest that commitment of mouse keratinocytes to terminal differentiation is independent of extracellular calcium and may be regulated primarily by extracellular factors other than calcium.

Developmental assembly of the renal microvascula- ture requires spatially and temporally coordina... more Developmental assembly of the renal microvascula- ture requires spatially and temporally coordinated migration, assembly, differentiation, and maturation of endothelial cells in the context of adjacent epithelial and mesangial cells. In this study, endothelial expression and distribution of the receptor tyrosine phosphatase ECRTP/DEP-1 were evaluated during and after developmental assembly of the renal microvascula- ture. Monoclonal antibodies against ECRTP/DEP-1 ectodo- main