Dervla M. Mellerick-Dressler, Ph.D.
Assistant Professor of Pathology
Campus Address:
8301B MSRB III,
1150 West Medical Center Drive,
Ann Arbor, Michigan 48109-0646
Phone: 734-936-8640/647-1642
Dervlam@umich.edu
Annual Report | Biography | Research Interests | Selected Publications
Departmental Annual Report
Brief Biography
Dr.
Mellerick-Dressler received her undergraduate and Masters degrees in Microbiology
from University College Cork, Ireland in 1978 and 1980. She received her
Ph.D. in Microbiology from the University of Pennsylvania in 1986. Dr.
Mellerick-Dresser did her post-doctoral training in cell biology
in the Max Planck Institute for Biophysical Chemistry in Goettingen from
1987-1989. Between 1991-1994 she was a staff fellow at the NIH laboratories
of Dr. Ward Odenwald and Dr. Marshall Nirenberg. From 1994-1999 Dr. Mellerick-Dressler
was an Assistant Research Scientist in the Dept of Pediatrics at the University
of Michigan, she became an Assistant professor in Pathology in 1999.
Dr. Mellerick-Dressler uses the fruit fly, Drosophila, to study the molecular
basis of neural stem cell patterning and differentiation.
Research Interests
Neural stem cell patterning and differentiation
The research in my lab focuses primarily on the molecular
basis for neural stem cell patterning using the fruit fly, Drosophila,
as our model organism. Hierarchical interactions of key regulators act
to restrict the potential of individual cells during neural development.
A paradigm for understanding these genes and their regulatory interactions
is to study their paralogs in a less complex organism with the eventual
aim of applying the knowledge obtained to the vertebrate counterparts.
Fortunately, critical aspects of regulatory networks are highly conserved
between fruit flies and man. In addition, the Drosophila embryonic CNS
is relatively simple and well understood. It consists of bilateral stripes
of neuroectodermal cells at either side of the ventral midline. A subset
of these cells form the stem cells or neuroblasts that divide to generate
neuronal and glial progeny. The positioning of the stem cell along the
anterior-posterior (A-P) and the dorsal-ventral (D-V) axis is critical
to its identity. We use a combination of fly genetic, molecular biological,
and cell biological techniques to address complex issues related to gene
function and regulation that are not easily accessible in vertebrate or
cell culture models.
Recently, we and others described three homeobox genes that are critical
for the specification of the ventral (vnd), intermediate (ind) and lateral
(msh) neural stem cells in Drosophila. The main focus of our current research
is the ventral nervous system defective (vnd) gene (also known as NK-2),
which encodes a homeodomain containing transcription factor. vnd is necessary
and sufficient to induce ventral stem cell fates and repress intermediate
fates within Drosophila CNS stem cells. To elucidate how this protein
can both activate and repress gene expression. We are using amino acid
sequence alignment of vnd from two Drosophila species, D. virilis and
D. melanogaster, to identify amino acid sub-domains that are conserved,
and thus potentially functionally important. Transient transfection assays
are being used to dissect the role of these conserved protein sub-domains.
Another project focuses on understanding how Epidermal Growth Factor (EGF)-mediated
phosphorylation of Vnd modulates this transcription factor’s activity.
In addition to vnd, EGF patterns ventral stem cells. EGF receptor mutants
have subtle patterning changes in ventral stem cells that may be due in
part to lack of EGF-mediated phosphorylation of Vnd. Several independent
observations suggest that EGF regulates Vnd. For instance, over-expression
of the EGF ligand, Spitz, leads to an expanded domain of Vnd expression
in Drosophila embryos. Moreover, Vnd isolated from embryos and tissue
culture cells is heavily phosphorylated. Finally, Vnd has five consensus
PXS/TP motifs that are conserved between D. virilis and D. melanogaster.
These are potential substrates of the Drosophila ERK-1 type MAP kinase,
Rolled, that mediates the EGF response. We used site directed mutagenesis
to generate Vnd with mutations in the candidate phosphoserine and phosphothreonine
residues that are substrates for the kinase. A combination of transfection
and transgenic gain-of-function assays are being used to identify the
mechanism of EGF-mediated regulation of Vnd.
Other projects in the lab focus on dissecting the regulatory regions of
the vnd gene, as well as determining the identity and role of downstream
target genes that are regulated by vnd. Finally, in collaborations with
vertebrate developmental biologists we are using the fruit fly as a tool
to probe the role of genes of unknown function in vertebrate development.
The genetic accessibility of the fruit fly, the range of cell-specific
markers available, and the availability of the Drosophila genome sequence
makes this organism highly relevant for dissecting complex aspects of
gene regulation and function.
Selected Publications
MELLERICK, DM and Victoria Modica. Regulated
vnd expression is required both neural and glial specification in Drosophila.
In Press. Journal of Neurobiology.
Mc Donald, J.A., Holbrook, S., Doe, C.Q and MELLERICK, D.M. (1998). Dorsoventral
patterning in the Drosophila central nervous system: the vnd homeobox
gene specifies ventral column identity. Genes and Development, 12, 3603-3612.
Weiss, J.B., von Ohlen, T, MELLERICK, D.M. Dressler, G., Doe, CQ., and
Scott, M.P.(1998) Dorsoventral patterning in the Drosophila central nervous
system: the intermediate neuroblasts defective homeobox gene specifies
intermediate column identity. Genes and Development, 12, 3591-3602.
Zhang, S.D. , Kassis, J.A., Olde, B., MELLERICK, D.M., and Odenwald, W
(1996). Pollux, a novel Drosophila adhesion molecule belongs to a new
family of proteins expressed in plants, yeast, nematodes and man. Genes
and Dev. 10, 1108-119.
MELLERICK, D.M. and Nirenberg, M. (1995). Dorsal-ventral patterning genes
restrict NK-2 homeobox gene expression to the ventral half of the central
nervous system of Drosophila embryos. Developmental Biology. 171, 306-316.