Wendy Hanna-Rose
Associate Professor of Biochemistry and Molecular Biology,
Associate Department Head for Undergraduate Studies
University Park, PA 16802
Research Interests
Molecular Genetics of Metabolism and Development in C. elegans
Research Summary
The overarching goal of the Hanna-Rose lab is to understand how development is genetically programmed. We use the development of the reproductive structures in the nematode Caenorhabditis elegans as a research model. C. elegans is a simple organism with few cells. Yet, its development and physiology are sufficiently complex to represent the major mechanisms in animal development and homeostasis. C. elegans has been a valuable model for probing both developmental mechanisms and the impact of metabolism and environment in aging and health, and principles deduced in this system are relevant to higher organisms, including humans.
1. Developmental and physiological roles of NAD+ biosynthetic pathways
Nicotinamide (NAM) and nicotinic acid (NA), which are forms of the essential vitamin B3, are precursors for biosynthesis of nicotinamide adenine dinucleotide (NAD+). NAD+ is a central molecule in metabolism and a co-substrate for NAD+ consuming enzymes that regulate key biological processes, such as longevity and stress responses. While the biochemistry of NAD+ biosynthesis from vitamin B3 is well studied, the biological impacts of disruption of this biosynthetic pathway in a multicellular organism are not. We have made the novel discovery that mutation of the first enzyme in the NAM to NAD+ salvage biosynthesis pathway (PNC-1) cause developmental and functional defects in organ systems and necrotic death of specific cells (Figure 1) in C. elegans. We aim to understand how perturbation of metabolism and / or NAD+ consumer activity during development contributes to the function of organ systems in adulthood and how PNC-1 activity may impact the ability of the organism to respond to cellular stress.
2. Tubulogenesis
Most of your organs require biological tubes to function. How do cells form tubes? There isn’t one answer to this question because the cell rearrangements contributing to tubulogenesis in different organs and even within different areas of a single biological tube are varied. We aim to understand molecular mechanisms directing the development of our “plumbing”, i.e., our biological tubes. By studying C. elegans vulval tubulogenesis, we recently revealed a novel mechanism for de novo lumen formation involving migration of a one cell through an epithelial cell layer and developed a model that requires phospholipase function for maintenance of this luminal space. Current research is aimed at testing this model.
3. Microtubule organization and organ architecture
A developmental progression of changes in cell morphology is associated with the distinct tissue architectures observed in distinct regions of the C. elegans gonad- from the mitotic zone where the germline stem cells reside, to the syncytial region where meiosis is initiated (Figure 2) to the proximal region where individual oocytes are formed. In collaboration with Dr. Melissa Rolls, we recently demonstrated that interactions between the nuclear envelope and the plasma membrane mediated by the microtubule network are critical to maintenance of gonad architecture in the syncytial gonad. We hypothesize that changes in the organization of the microtubule cytoskeleton underlie the changes in architecture observed at the transition from the syncytial zone to the oocyte region. Current research is aimed at understanding establishment and regulation of the microtubule cytoskeleton in this organ.
Figure 1. The uv1 cells swell dramatically and necrose in a pnc-1 mutant animal.
Figure 2. Syncytial region of the C. elegans gonad. The plasma membranes (green) partially encase individual nuclei (blue). Cytoplasm is shared between nuclei and the central rachis, which is devoid of nuclei or membranes.
Representative Publications
- Tracy L. Vrablik, Wenqing Wang, Awani Upadhyah and Wendy Hanna-Rose (2010) Muscle type-specific responses to NAD+ salvage biosynthesis promote muscle function in Caenorhabditis elegans. Dev Biol. 2010 Nov 16. [Epub ahead of print]PMID: 21092737
- JB French, Y. Cen, Tracy L. Vrablik, P Xu, E. Allen, Wendy Hanna-Rose, Anthony A Sauve. (2010) Characterization of nicotinamidases: steady state kinetic parameters, classwide inhibition by nicotinaldehydes, and catalytic mechanism. Biochemistry 49(49):10421-39.
- Kang Zhou and Wendy Hanna-Rose (2010) Movers and shakers of anchored: Caenorhabditis elegans nuclei achieve it with KASH/ SUN. Dev Dyn. 239(5):1352-64.
- IL Minn, Melissa Rolls, Wendy Hanna-Rose and Christian J. Malone (2009) SUN-1 and ZYG-12, mediators of centrosome-nucleus attachment, are a functional SUN/KASH pair in Caenorhabditis elegans. Mol Biol Cell 20(21):4586-95.
- Tracy L. Vrablik, Li Huang, Stephanie E. Lange and Wendy Hanna-Rose (2009) Nicotinamidase modulation of NAD+ biosynthesis and nicotinamide levels separately affect reproductive development and cell survival in C. elegans. Development 136(21):3637-3646.
- Kang Zhou, Melissa M. Rolls, David H. Hall, Christian J. Malone and Wendy Hanna-Rose (2009) A ZYG-12-dynein interaction at the nuclear envelope defines cytoskeletal architecture in the C. elegans gonad. Journal of Cell Biology 186(2) 229-41.
- Kathleen A. Estes and Wendy Hanna-Rose (2009) The anchor cell initiates dorsal lumen formation during C. elegans vulval tubulogenesis. Developmental Biology 328(2):297-304.
- Ryan W. Johnson, Leah Y. Liu, Wendy Hanna-Rose, and Helen M. Chamberlin (2009) The C. elegans heterochronic gene lin-14 coordinates temporal progression and maturation in the egg-laying system. Developmental Dynamics 238(2):394-404.
- Nicholas N. Lyssenko, Yana Miteva, Simon Gilroy, Wendy Hanna-Rose, and Robert A. Schlegel (2008) An unexpectedly high degree of specialization and a widespread involvement in sterol metabolism among the C. elegans putative aminophospholipid translocases. BMC Developmental Biology 8 (1):96.
- Nicholas N. Lyssenko, Wendy Hanna-Rose, and Robert A. Schlegel. (2007) A cognate putative nuclear localization signal effects strong nuclear localization of a GFP reporter and facilitates gene expression studies in C. elegans. BioTechniques 43(5):596-600.
- Kathleen A. Estes, Rasika Kalamegham, and Wendy Hanna-Rose. (2007) Membrane localization of the NlpC/P60 family protein EGL-26 correlates with regulation of vulval cell morphogenesis in C. elegans". Developmental Biology 308(1):196-205.
- Hongliu Sun, Brian L. Nelms, Sama F. Sleiman, Helen M. Chamberlin and Wendy Hanna-Rose. (2007) Genetic modulation of gene activity in C. elegans by HIM-8 and related C2H2 zinc finger proteins. Genetics 177(2):1221-6.
- Li Huang and Wendy Hanna-Rose. (2006) EGF signaling overcomes a uterine cell death associated with temporal mis-coordination of organogenesis within the C. elegans egg-laying apparatus. Developmental Biology 300(2):599-611.
- Brian Nelms and Wendy Hanna-Rose. (2006) C. elegans HIM-8 has a meiosis-independent function in antagonizing the activity of the EGL-13 Sox protein. Developmental Biology 293(2): 392-402.
