Daniel R. Marenda, Ph.D.
Assistant
Professor of Biology
Education
Ph.D., Syracuse University
Post-doc,
Emory University School of Medicine, 2003-2006
Address
University
of the Sciences in Philadelphia
McNeil
Science and Technology
Building
600 South 43rd
Street
Philadelphia , PA
19104
Phone:
215-596-8923
e-mail: d.marend@usip.edu
|
Daniel R. Marenda, Ph.D. Assistant
Professor of Biology
Education Ph.D., Post-doc,
Emory University School of Medicine, 2003-2006 |
|
Address University
of the Sciences in McNeil
Science and Phone:
215-596-8923 e-mail: |
Research
Interests
1) Retinal Neurogenesis: A fundamental question
in developmental biology is the control of neurogenesis. Proper neural development underlies the
basic cellular processes required within all cells of the mature nervous
system. Neurophysiology,
and even broader processes such as consciousness or intelligence intimately
depend upon proper developmental control of cells within the nervous
system. The long term goal of this
aspect of our research is a deeper understanding of retinal neurogenesis, with the hope that this research will
ultimately lead to new diagnostic tools and/or therapeutic targets for
retinal regeneration in patients with inherited retinal degeneration or
damage.
|
Research
Interests 1) Retinal Neurogenesis: A fundamental question
in developmental biology is the control of neurogenesis. Proper neural development underlies the
basic cellular processes required within all cells of the mature nervous
system. Neurophysiology,
and even broader processes such as consciousness or intelligence intimately
depend upon proper developmental control of cells within the nervous
system. The long term goal of this
aspect of our research is a deeper understanding of retinal neurogenesis, with the hope that this research will
ultimately lead to new diagnostic tools and/or therapeutic targets for
retinal regeneration in patients with inherited retinal degeneration or
damage. |
The developing eye of the fruit-fly Drosophila melanogaster
serves as an excellent system to model how neurogenesis
is controlled within a developing nervous tissue. The adult Drosophila eye consists of approximately 800 unit eyes (ommatidia), each of which requires exquisite precision
in their morphology for proper function.
This morphological exactness requires precision in development, as
any disruption in this process can be seen externally in the adult eye
itself.
|
The developing eye of the fruit-fly Drosophila melanogaster
serves as an excellent system to model how neurogenesis
is controlled within a developing nervous tissue. The adult Drosophila eye consists of approximately 800 unit eyes (ommatidia), each of which requires exquisite precision
in their morphology for proper function.
This morphological exactness requires precision in development, as
any disruption in this process can be seen externally in the adult eye
itself. |
Proper retinal neurogenesis
in Drosophila begins with the
induction of the founding neural cell type in the retina through the precise
expression of the proneural transcription factor atonal (ato). Figure A illustrates Atonal
protein expression in the developing fly retina imaginal
disc. This expression is critical,
as disruption of ato
leads to morphological disruptions of eye development, while complete loss
of ato
leads to the complete loss of the eye (see image below).
|
Proper retinal neurogenesis in Drosophila begins with the induction of the founding neural cell type in the retina through the precise expression of the proneural transcription factor atonal (ato). Figure A illustrates Atonal protein expression in the developing fly retina imaginal disc. This expression is critical, as disruption of ato leads to morphological disruptions of eye development, while complete loss of ato leads to the complete loss of the eye (see image below). |
In our lab, we take a genetic approach to
understanding the mechanisms that control Drosophila retinal neurogenesis by undertaking
genetic modifier screens based on an ato loss-of-function genotype that displays a rough eye phenotype
(see panels D-F above), and results in decreased Atonal protein expression
(see panels G-I above).
There are striking similarities between fly and
vertebrate eye development. The
process of specifying and spacing the first retinal neural cell type (the
R8 photoreceptor in flies and the Retinal Ganglion Cell in humans) is very
well conserved and of particular interest in our lab. In vertebrates, expression of bHLH transcription factors orthologous
to Drosophila Atonal
(MATH5/Atoh7, XATH5, ATH5) and their progressive
restriction are also involved in specifying the retinal ganglion cells, the
founding neural cell type in mammals. Thus, a more complete understanding
of what transcription factors are required for R8 specification in Drosophila eye development, and how
and when these transcription factors regulate Atonal expression will likely
be of very broad relevance to our understanding of the process of mammalian
retinal development.
|
In our lab, we take a genetic approach to
understanding the mechanisms that control Drosophila retinal neurogenesis by undertaking
genetic modifier screens based on an ato loss-of-function genotype that displays a rough eye phenotype
(see panels D-F above), and results in decreased Atonal protein expression
(see panels G-I above). |
|
There are striking similarities between fly and
vertebrate eye development. The
process of specifying and spacing the first retinal neural cell type (the
R8 photoreceptor in flies and the Retinal Ganglion Cell in humans) is very
well conserved and of particular interest in our lab. In vertebrates, expression of bHLH transcription factors orthologous
to Drosophila Atonal
(MATH5/Atoh7, XATH5, ATH5) and their progressive
restriction are also involved in specifying the retinal ganglion cells, the
founding neural cell type in mammals. Thus, a more complete understanding
of what transcription factors are required for R8 specification in Drosophila eye development, and how
and when these transcription factors regulate Atonal expression will likely
be of very broad relevance to our understanding of the process of mammalian
retinal development. |
Research
Interests
2) Cell division, cell
growth, and cell differentiation, and their misregulation
in cancer: A striking fact of development is that all
multi-cellular animals develop from a single cell. It is the burden of this single cell to
coordinate and control a large number of diverse cellular processes as it
develops, in order to properly form a viable, fully functional organism. So important is the success
of this basic developmental progression, that mis-regulation
of many of these basic processes are a contributing factor to human
disease. However, even with the
diverse array of cellular processes required for proper development to
occur, only a comparatively small number of developmental signals are
required to control development. As
such, reiterative activation of the same signaling pathways is used to
elicit multiple and distinct cellular functions. Our long term goal for this aspect of our
research is a deeper understanding of the regulation of one of these
developmental signals: the Ras/MAPK signal
transduction pathway. Proper
activation of Ras/MAPK is required for a broad
number of developmental processes, including cell division, growth, and
differentiation. In fact, mis-regulation of this pathway is associated with
approximately 25% of human cancers.
Thus, a more comprehensive knowledge of how this pathway
discriminates between the processes of cell growth, division, and
differentiation is necessary for a full understanding of this disease.
Figures
B-I show mutations in a few genes of interest in our lab that are able to
genetically enhance our atonal loss-of-function
phenotype in the eye. We are
particularly interested in the analysis of the lilliputian gene (lilli, panels B-C), mutations in which are involved in FRAXE, the most common form of hereditary non-syndromic
mental retardation, affecting approximately 1 in 50,000 males. We believe that by understanding how
these genes regulate neurogenesis in the
developing fly eye, we can better understand each gene’s function in the
control of proneural gene expression and the
development of other neurological tissues.
|
Research
Interests 2) Cell division, cell
growth, and cell differentiation, and their misregulation
in cancer: A striking fact of development is that all
multi-cellular animals develop from a single cell. It is the burden of this single cell to
coordinate and control a large number of diverse cellular processes as it
develops, in order to properly form a viable, fully functional organism. So important is the success
of this basic developmental progression, that mis-regulation
of many of these basic processes are a contributing factor to human
disease. However, even with the
diverse array of cellular processes required for proper development to
occur, only a comparatively small number of developmental signals are
required to control development. As
such, reiterative activation of the same signaling pathways is used to
elicit multiple and distinct cellular functions. Our long term goal for this aspect of our
research is a deeper understanding of the regulation of one of these
developmental signals: the Ras/MAPK signal
transduction pathway. Proper
activation of Ras/MAPK is required for a broad
number of developmental processes, including cell division, growth, and
differentiation. In fact, mis-regulation of this pathway is associated with
approximately 25% of human cancers.
Thus, a more comprehensive knowledge of how this pathway
discriminates between the processes of cell growth, division, and
differentiation is necessary for a full understanding of this disease.
|
|
Figures
B-I show mutations in a few genes of interest in our lab that are able to
genetically enhance our atonal loss-of-function
phenotype in the eye. We are
particularly interested in the analysis of the lilliputian gene (lilli, panels B-C), mutations in which are involved in FRAXE, the most common form of hereditary non-syndromic
mental retardation, affecting approximately 1 in 50,000 males. We believe that by understanding how
these genes regulate neurogenesis in the
developing fly eye, we can better understand each gene’s function in the
control of proneural gene expression and the
development of other neurological tissues.
|
Our initial investigations into the regulation
of Ras/MAPK activity in the control of cell
division, growth, and differentiation in the wing began with an analysis of
the subcellular localization of the MAPK
protein. We had utilized both an
antibody that specifically recognizes the phosphorylated
form of MAPK (pMAPK in red in Figure to the
left), and a group of MAPK fusion proteins that detects the nuclear
translocation of MAPK in vivo
(green dots in figure to the left).
|
Our initial investigations into the regulation
of Ras/MAPK activity in the control of cell
division, growth, and differentiation in the wing began with an analysis of
the subcellular localization of the MAPK
protein. We had utilized both an
antibody that specifically recognizes the phosphorylated
form of MAPK (pMAPK in red in Figure to the
left), and a group of MAPK fusion proteins that detects the nuclear
translocation of MAPK in vivo
(green dots in figure to the left). |
Using these two reagents, we determined that pMAPK is held in the cytoplasm of some developing wing
cells, and that this ‘cytoplasmic hold’ directs
wing cells to differentiate as adult vein tissue. At the same time, MAPK does move into the
nucleus of other wing cells, and this nuclear translocation promotes these
cells to proliferate. Thus, the
proper regulation of the subcellular localization
of MAPK during wing development is critical to elicit appropriate cellular
responses required for normal wing patterning. We are continuing to analyze how the subcellular localization of MAPK is regulated in fly
tissues, and how its misregulation is associated
with abnormal growth, division, and development.
|
Using these two reagents, we determined that pMAPK is held in the cytoplasm of some developing wing
cells, and that this ‘cytoplasmic hold’ directs
wing cells to differentiate as adult vein tissue. At the same time, MAPK does move into the
nucleus of other wing cells, and this nuclear translocation promotes these
cells to proliferate. Thus, the
proper regulation of the subcellular localization
of MAPK during wing development is critical to elicit appropriate cellular
responses required for normal wing patterning. We are continuing to analyze how the subcellular localization of MAPK is regulated in fly
tissues, and how its misregulation is associated
with abnormal growth, division, and development. |
Marenda lab:
P.I. / C.O. : Captain Daniel R. Marenda
Second
in Command Undergraduate
Students
Commander Ginnene
Middleton (Lab Manager) Lt. Junior Grade Andrew Gangemi
Lt. Junior Grade Arpit Shah
Post-doctoral
Fellows Lt. Junior Grade David Melicharek
Lt. Commander Gerardo Paez, Ph.D. ensign Viveck Daftary
ensign Luke Baird
Graduate
Students
Lieutenant Neena
Majumdar One
very special High School Senior
Lieutenant Shivangi
Inamdar Chief Petty Officer Andrew Orapallo
|
P.I. / C.O. : Captain Daniel R. Marenda Second
in Command Undergraduate
Students Commander Ginnene
Middleton (Lab Manager) Lt. Junior Grade Andrew Gangemi Lt. Junior Grade Arpit Shah Post-doctoral
Fellows Lt. Junior Grade David Melicharek Lt. Commander Gerardo Paez, Ph.D. ensign Viveck Daftary ensign Luke Baird Graduate
Students Lieutenant Neena
Majumdar One
very special High School Senior Lieutenant Shivangi
Inamdar Chief Petty Officer Andrew Orapallo |
Publications
1) Howell
N, Bogolin C, Jamieson R, Marenda DR, and
Mackey DA (1998) mtDNA mutations that cause Optic
Neuropathy: How do we know? Am. J. Hum. Genet. 62:
196-202
2)
Marenda DR,
Zraly CB, Feng Y, Egan S,
and Dingwall AK (2003) The Drosophila SNR1 (SNF5/INI1) subunit directs
essential developmental functions of the Brahma chromatin remodeling complex.
Mol. Cell. Biol. 23: 289-305
3) Zraly CB, Marenda DR,
Nanchal R, Cavalli G, Muchardt C, and Dingwall AK (2003) SNR1 is an essential component
in a subset of Drosophila Brm complexes,
targeting specific functions during development. Dev. Biol. 253: 291-308
5) Zraly CB,
*6) Marenda DR, Vrailas AD, Rodrigues AB, Cook S, Powers MA, Lorenzen
JA, Perkins LA, and Moses K. (2006) MAP kinase subcellular localization controls both pattern and
proliferation in the developing Drosophila wing. Development 133: 43-51
* Highlighted
“In this issue” in Development 133:
102e
*Noted in Faculty of
1000 Biology http://www.facultyof1000.com/article/16308331/evaluation
7) Vrailas AD,
8) Vrailas AD, Majumdar N,
Middleton G, Cooke EM, and Marenda DR
(2007) Delta and Egfr expression are regulated by
Importin-7/Moleskin in Drosophila
wing development. Dev. Biol. 308: 534-546
9) Melecharek D, Shah A, Middleton G, Gangemi AJ, Cooke EM, Alysia D. Vrailas, and
10) Mortimer NM,
Moberg KH, Paez G, Perkins LA, and Marenda DR. (2007) dpp/thickveins signaling
regulates tracheal cell specification through MAP kinase
subcellular localization in the developing Drosophila embryo. (In preparation)
11) Chakraborty R, Bowser K, Patel N, Pagano
D, Pontano L, Cuellar TL, Moir
R, Gangemi AJ, Middleton G, Marenda DR, Lee J,
and Saunders AJ. (2007) “In Vitro Caloric Restriction Induces SirT1 to
modulate APP Metabolism” (In preparation)
Teaching
BS
767: Cell Biology Methods Laboratory
BS
763: Cell Biology Methods Lecture
BS
860: Special Topics in Cancer Biology