Dr Annemiek Beverdam

Developmental and Regenerative Dermatology Unit

DR ANNEMIEK BEVERDAM - DEVELOPMENTAL AND REGENERATIVE DERMATOLOGY UNIT

 

Research Interests

Biography

Qualifications

Research Projects in Developmental and Regenerative Dermatology Unit

Bibliography

Undergraduate, Postgraduate and Postdoc Research Opportunities

Membership in Societies

Contact Details

Group members

Research funding

 

 

WE ARE CURRENTLY RECRUITING HONOURS AND PHD STUDENTS TO START IN 2017. PLEASE CONTACT ANNEMIEK FOR MORE INFORMATION.

 

Research Interests:

Dr. Beverdam studies the genetic processes that govern development, homeostasis and regeneration of the skin in the mouse. Her research aims at understanding the genetic and molecular basis of developmental and human regenerative skin diseases such as skin cancer, which affects 2 out of 3 Australians in their life time.

She recently made the pivotal discovery that Yes-associated protein (YAP) functions as a key molecular switch in epidermal stem/progenitor cell proliferation and differentiation (Beverdam et al., JID 2013). Dr. Beverdam currently investigates the developmental genetic context in which YAP functions to control skin stem/progenitor cells in normal and in disrupted skin biology. She employs genetically manipulated mouse models, human skin samples, advanced imaging technology such as confocal microscopy and whole mouse in vivo imaging, gene and protein expression analyses and whole genome approaches to address her research questions. Her research will open up exciting new avenues for translational research and the development of treatments for human regenerative skin disease.

 

 

Biography:

Dr. Annemiek Beverdam is a developmental geneticist with special interest in epidermal development and regeneration in the mouse, and in the genetic basis of human regenerative skin disease.

She obtained her PhD at the Hubrecht Institute in The Netherlands in 2001. Subsequently, she performed her postdoctoral research at the National Cancer Institute in Genoa, Italy, and at the Institute of Molecular Biosciences The School of Biomedical Sciences at The University of Queensland. She was appointed as Lecturer as a Strategic Recruit at UNSW Australia in July 2013, and she was promoted to Senior Lecturer in Anatomy in July 2015. She currently is Head of the Developmental and Regenerative Dermatology Laboratory at the School of Medical Sciences, UNSW Australia, and has 21 peer-reviewed publications in leading journals in her field.

The primary research focus of her lab is the genetic and molecular context in which Yes-associated protein (YAP) functions to control normal epidermal homeostasis, how these processes go awry in regenerative skin diseases such as skin cancer, and to identify avenues to cure these disorders. Her research is funded by the NHMRC and is part of a larger, long-term and ambitious goal to identify key genes linking stem cell biology to organ size and growth.

 

Qualifications:

MSc (Biomedical Sciences, Utrecht University, The Netherlands)

PhD (Hubrecht Institute for Developmental Biology and Stem Cell Research/Utrecht University, The Netherlands)

 

Research Projects in Developmental and Regenerative Dermatology Unit:

  1. Genetic regulation of skin stem/progenitor cell proliferation
  2. Role of YAP in skin tumorigenesis
  3. Role of YAP in human regenerative skin disease
  4. Identification of upstream regulators of YAP activity in skin biology
  5. In vivo skin imaging technology in whole mice

Research Project 1: Genetic regulation of skin stem/progenitor cell proliferation

We have recently identified that the transcriptional co-activator YAP is an important activator of skin cell division. However, the developmental genetic pathways in which YAP acts to control these growth processes remain mostly unknown.

In this project we seek out the developmental genetics context in which YAP acts to control skin stem/progenitor cell proliferation. We are particularly interested in understanding how YAP interacts with two prominent growth regulating pathways, the Wnt and the Hedgehog pathways. We employ complex mouse genetics using transgenic and conditional loss of function mutant mouse models, histology, gene and protein expression analyses, confocal and in vivo imaging technology, and quantitative real time RTPCR assays to answer our research questions. These studies will give us important new insights into the genetic etiology of human skin disease. (Collaboration with A/Prof Khosrotehrani (UQCCR) and Professor Brandon Wainwright (IMB)).

Key contact: Dr Annemiek Beverdam, Faculty of Medicine.

Project team: Mr. Bassem Akladios, Ms Veronica Mendoza-Reinoso, Ms Nichole Giles, Dr. Annemiek Beverdam, Dr Jason Cain (Hudson), Dr Michael Samuel (CCB, Adelaide), A/Prof Khosrotehrani (UQCCR), Professor Neil Watkins (Garvan).

Hyperproliferative epidermal stem/progenitor cells in mice overexpressing hyperactive YAP

 

Research Project 2: Role of YAP in skin tumorigenesis

Australia has the highest skin cancer incidence in the world, and 2 out of 3 Australians will be affected in their life time. Skin cancer is caused by the uncontrolled proliferation of skin cells, and their transformation into aggressive invasive cells that spread through the blood and lymphatic systems to distant organs and tissues, eventually resulting in the formation of metastases that compromise organ and tissue function, ultimately resulting in death.

We have recently identified that transcriptional co-activator YAP is an important activator of skin cell division. We also found activation of YAP in the cells of many types of human skin tumors. However, the developmental genetic pathways in which YAP acts to control these growth processes remain unknown.

In this project we perform skin tumorigenesis assays using a YAP gain of function mouse model. We perform whole mouse assays and skin transplantation tumorigenesis assays. We employ basic histology, gene and protein expression analyses and confocal microscopy to assess skin tumors. We also perform genomic approaches and look for common transcriptional signatures in tumors of transgenic vs. wildtype mice. This project will provide novel insights into the role of YAP and its downstream targets in skin tumorigenesis. This will yield possible therapeutic targets to treat human skin cancer.

Key contact: Dr Annemiek Beverdam, Faculty of Medicine.

Project team: Bassem Akladios, Ms Veronica Mendoza, Dr. Annemiek Beverdam, Dr. Michael Samuel (CCB, Adelaide), Professor Peter Gunning (UNSW Australia), Professor Peter Soyer, Dr. Duncan Lambie (UQ).

YAP is expressed in human skin cancer

 

Research Project 3: Role of YAP in human regenerative skin disease

In this project we want to study the role of YAP in human regenerative skin disease. We assess YAP activation in skin biopsies of human patients with regenerative skin disease. We will employ routine histology, and gene and protein expression studies. In addition, we will manipulate YAP activity in explants and keratinocytes of primary skin samples and assess the effects on the disease progression.

Key contact: Dr Annemiek Beverdam, Faculty of Medicine.

Project team: Ms Veronica Mendoza-Reinoso, Dr. Annemiek Beverdam, Faculty of Medicine UNSW, Dr Ben Roediger, Centenary Institute, Sydney, Dr. John Common, A* Star, Singapore.

 

Research Project 4: Identification of upstream regulators of YAP activity in skin biology

In this project we want to understand the upstream regulatory mechanisms that control YAP/TEAD activity in skin stem/progenitor cell proliferation, and how to manipulate these genetically or using drugs to interfere with YAP/TEAD transcriptional activity. To do this, we generate a read out system for YAP/TEAD activity. We will perform (high throughput) in vitro studies using cultured keratinocytes and drug, siRNA and lentiviral libraries. In addition, we will generate an in vivo read out system for YAP/TEAD activity in the mouse epidermis studies and employ (in vivo) confocal and in vivo imaging technologies. These studies will yield exciting candidates for future human clinical trials that test the therapeutic value of the drug in human skin cancer treatment and other regenerative dermatological diseases.

Key contact: Dr Annemiek Beverdam, Faculty of Medicine.

Project team: Ms Nichole Giles, Dr. Annemiek Beverdam, UNSW.

 

 

Research Project 5: In vivo skin imaging technology in whole mice

In this project we aim to develop and refine non-invasive skin imaging technology, which will aid in the early detection of human regenerative skin disease. We will employ in vivo bioluminescence imaging and MRI using genetically modified mouse lines that express fluorescent and/or bioluminescent reporters and with skin abnormalities.

Key contact: Dr Annemiek Beverdam, Faculty of Medicine.

Project team: Mr Bassem Akladios, Dr. Annemiek Beverdam.

 

 

Group Members:

WE ARE CURRENTLY RECRUITING HONOURS AND PHD STUDENTS STARTING IN 2018. PLEASE CONTACT ANNEMIEK FOR MORE INFORMATION.

 

Ms Nichole Giles, PhD student (2017 - 2020), Australian Postgraduate Award scholarship

Mr Bassem Akladios, PhD student (2014 - 2017), University International Postgraduate Award (UIPA) 

Ms Veronica Mendoza, PhD student (2014 - 2017), FINCyT scholarship (Peru) and TFS scholarship (UNSW)

Mr Tony Wang, 2017 BHons student

 

Lab alumni:

Dr Anne-Marie Mooney

Dr Ngan Chen

Dr Tam Dinh Nguyen

Ms Nivedha Saravanan

Ms Lakshini Ranganathan

Ms Emma Singer

Ms Jin Lim

Ms Yvonne Gathier (University of Groningen, The Netherlands)

Ms Michelle Lin

Mr Jose Alberto Loro Pinzon (Brasil)

 

Research funding:

NHMRC 'New Investigator' Project Grant 2014 - 2017: 'YAP and the Wnt pathway in skin biology. $383,447

MREII equipment grant 2015, Beverdam et al. 'Essential high-end equipment to enable non-routine histological procedures for morphology and protein and RNA expression analyses in mouse, rat and human tissue sections in vivo'. $93,527

MREII equipment grant 2015: Whan et al., Zeiss Light sheet microscope. $575,000

 

Bibliography:

http://www.ncbi.nlm.nih.gov/pubmed/?term=beverdam+a

 

Refereed research articles:

Bassem Akladios, Veronica Mendoza-Reinoso, Jason E. Cain, Taopeng Wang, Duncan L. Lambie, D. Neil Watkins and Annemiek Beverdam. Positive Regulatory Interactions between YAP and Hedgehog Signalling in Skin Homeostasis and BCC Development in Mouse Skin in vivo. PLoS ONE, accepted for publication.

Susan Maree Corley; Karen L MacKenzie; Annemiek Beverdam; Louise F Roddam; Marc R Wilkins (2017). Differentially expressed genes from RNA-Seq and functional enrichment results are affected by the choice of single-end versus paired-end reads and stranded versus non-stranded protocols. BMC Genomics, 2017 May 23;18(1):399. doi: 10.1186/s12864-017-3797-0.

Akladios B., Mendoza-Reinoso V., Samuel MS.,  Hardeman E., Khosrotehrani K., Key B; Beverdam A (2017). ‘Epidermal YAP2-5SA-ΔC Drives β-Catenin Activation to Promote Keratinocyte Proliferation in the Mouse Skin in vivo’. The Journal of Investigative Dermatology.

Liang H*, Akladios B*, Canales CP*, Francis R, Hardeman EH, Beverdam A. CUBIC protocol visualizes protein expression at single cell resolution in whole mount skin preparations (2016). JoVE doi:10.3791/54401.

Corley SM, Canales C, Carmona-Mora P, Mendoza-Reinoso V, Beverdam A, Hardeman EH, Wilkins M, Palmer S. (2016). RNA-Seq analysis of Gtf2ird1 knockout epidermal tissue provides potential insights into molecular mechanisms underpinning Williams-Beuren syndrome. BMC Genomics.

James G., Key B., Beverdam A. (2014). The E3 ubiquitin ligase Mycbp2 genetically interacts with Robo2 to modulate axon guidance in the mouse olfactory system. Brain Structure and Function. Volume 219, Issue 3, Page 861-874. Impact Factor: 7.8. (Link to PubMed)

James G., Foster SR., Key B., Beverdam A. (2013). The Expression Pattern of EVA1C, a Novel Slit Receptor, Is Consistent with an Axon Guidance Role in the Mouse Nervous System. PLoS One, Sep 9;8(9):e74115. doi: 10.1371/journal.pone.0074115. Impact Factor: 3.8. (Link to PubMed)

Beverdam A., Claxton C., Zhang., X., James G., Harvey KF, Key B. (2013). YAP controls stem/progenitor cell proliferation in the mouse postnatal epidermis. Journal of Investigative Dermatology, Impact factor 6.3. (Link to PubMed)

Beverdam A, Svingen T, Bagheri-Fam S, McClive P, Sinclair AH, Harley VR, Koopman P. (2010). Protein tyrosine kinase 2 beta (PTK2B), but not focal adhesion kinase (FAK), is expressed in a sexually dimorphic pattern in developing mouse gonads. Dev Dyn. 239: 2735-41. Impact factor 3.0. (Link to PubMed)

Beverdam A., Svingen T., McClive P., Bernard P., Bagheri-Fam S., Robson M., Banan M., Banan M., Harley V., Sinclair A., and Koopman P. (2009). Gstm6 is a Sox9-responsive gene expressed in Sertoli cells during testis development in mice. Reproduction, 137: 481-486Impact factor 3.4 (Link to PubMed)

Svingen T., Beverdam A., Bernard P., McClive P., Harley V.R., Sinclair A.H., and Koopman, P. (2007) Sex-specific expression of a novel gene Tmem184a  during mouse testis differentiation. Reproduction, 133: 983-9. Impact Factor: 3.4. (Link to PubMed)

Little M.H., Brennan J., Georgas K., Davies J.A., Davidson D.R., Baldock R.A., Beverdam A., et al., (2007) A high-resolution anatomical ontology of the developing murine genitourinary tract. Gene Expression Patterns, 7, 680-699. Impact Factor: 2.2. (Link to PubMed)

Svingen T., Beverdam A., Verma P., Wilhelm D., and Koopman. P. (2007). Aard is specifically up-regulated in Sertoli cells of the fetal and adult mouse testis. Int. J. Dev. Biol. 51, 255-258. Impact Factor: 3.0. (Link to PubMed)

Beverdam A., and Koopman P. (2006). Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes, Hum Mol Genet. 15: 417-431. Impact Factor: 8.1. (Link to PubMed)

Levi G, Mantero S., Barbieri O., Cantatore D., Paleari L., Beverdam A., Genova F., Robert B., and Merlo G.R. (2006). Msx1 and Dlx5 act independently in development of craniofacial skeleton, but converge on the regulation of Bmp signaling in palate formation. Mech Dev. 123: 3-16. Impact Factor: 3.5. (Link to PubMed)

Wilhelm D., Martinson F., Bradford S., Wilson M.J., Combes A.N., Beverdam A., Bowles J., Mizusaki H., and Koopman P. (2005). Sertoli cell differentiation is induced both cell-autonomously and throaugh prostaglandin signaling during mammalian sex determination. Dev Biol. 287: 111-124. Impact Factor: 4.4. (Link to PubMed)

Kuijper S., Beverdam A., Kroon C., Brouwer A., Candille S., Barsh G. and Meijlink F. (2005). Genetics of shoulder girdle formation: roles of Tbx15 and aristaless-like genes. Development 132:1601-1610. Impact Factor: 7.6. (Link to PubMed)

Loffler K. A., Combes A.N., Wilhelm D., Beverdam A., Bowles J. and Koopman P. (2005). Pisrt1, a gene implicated in XX sex reversal, is expressed in gonads of both sexes during mouse development. Mol Genet Metab. 86: 286-292. Impact Factor: 2.6. (Link to PubMed)

Beverdam A., Wilhelm D. and Koopman P. (2003). Molecular characterization of three gonad cell lines. Cytogenet and Genome Res 101: 242-249. Impact Factor: 2.4. (Link to PubMed)

Beverdam A., Merlo G.R., Paleari L., Mantero S., Genova F., Barbieri O., Janvier P. and Levi G. (2002). Jaw transformation with gain of symmetry after Dlx5/Dlx6 inactivation. Mirror of the past? Genesis 34: 221-227. Impact Factor: 2.5. (Link to PubMed)

Merlo G., Paleari L., Genova F., Mantero S., Beverdam A., Palmisano G.L., Barbieri O. and Levi G. (2002). A mouse model of Split Hand/Foot Malformation Type I. Genesis 33: 97-101. Impact Factor: 2.5. (Link to PubMed)

Beverdam A., Brouwer A., Reijnen M., Korving J. and Meijlink F. (2001). Severe nasal clefting and abnormal embryonic apoptosis in Alx3/Alx4 double mutant mice. Development 128, 3975-3986. Impact Factor: 7.6. (Link to PubMed)

Beverdam A. and Meijlink F. (2001). Expression patterns of group-I aristaless-related genes during craniofacial and limb development. Mech. Dev. 107, 163-167. Impact Factor: 3.2. (Link to PubMed)

 

Refereed reviews:

Meijlink F., Beverdam A., Brouwer A., Oosterveen T.C. and Ten Berge D. (1999). Vertebrate aristaless-related genes. Int. J. Dev. Biol. 43, 651-663. Impact Factor: 2.8. (Link to PubMed)

 

Books and book chapters:

Merlo G.R., Beverdam A. and Levi G. (2003) Murine Homeobox gene control of embryonic patterning and organogenesis. “Advances in Developmental Biology and Biochemistry”. Chapter 4 (T. Lufkin, ed) Adv. Develop. Biol. Biochem. 13: 107-132.

Beverdam A. (2001). Functions of Alx3, Alx4 and Cart1 during craniofacial development in the mouse. Doctoral thesis.

 

Undergraduate, Postgraduate and Postdoc Research Opportunities:

Enthusiastic, bright and hard-working undergraduate and postgraduate students and postdocs who are interested in research projects that concern the developmental and regenerative biology of the skin, should contact Dr. Annemiek Beverdam for further information. (A.Beverdam@unsw.edu.au)

 

Membership in Societies:

  • Australian and New Zealand Society for Cell and Developmental Biology (Society Secretary 2015-2017; NSW state representative 2013-2015; QLD state representative 2011-2013)
  • Australasian Society for Stem Cell Research
  • Australian Society for Dermatology Research
  • Society for Developmental Biology

 

Contact Details:

Annemiek Beverdam, PhD

Senior Lecturer, Head of the Developmental and Regenerative Dermatology Unit (DRDU)

Wallace Wurth Building East (C27),  Level 2, Rm 234

School of Medical Sciences

UNSW Australia

Sydney NSW2052

Australia

 

Email: A.Beverdam@unsw.edu.au

Phone: +61 (0)2 9385 0019

Mobile: +61 (0)431 146132

Fax: +61 (0)2 9385 0022

Project team

Dr Annemiek Beverdam
Faculty of Medicine

Project collaborators: External

Professor Brian Key
School of Biomedical Sciences, The University of Queensland
Professor Peter Soyer
School of Medicine, The University of Queensland
Dr Michael Samuel
Centre for Cancer Biology, SA Pathology
Dr Ben Roediger
Centenary Institute

Key contact

Faculty of Medicine
02 93850019
A.Beverdam@unsw.edu.au