About Professor Hans Zoellner

I am interested in how biological form and function influence each other, especially how individual cells arrange themselves to form coherent functional tissues. I have studied this fundamental question largely in context of the circulation. Changes in microvascular shape are especially apparent in inflammation, wound healing and cancer, so these have been studied as biologically relevant examples. More recent work also looks at bone remodelling and scarring diseases. My team of students, post-doctoral and academic colleagues, explore what we find to be exciting scientific questions using a wide range of standard and cutting edge laboratory and analytical techniques. We increasingly use engineering tools and approaches to think about biological form, so that much of our current and ongoing work is in collaboration with the Faculty of Engineering. Emerging from our relationship with Engineering, has been an exciting new line of study, still at an early stage, developing dental applications for robotics. My research philosophy is to be led by our own observations, as opposed to the fashion of the day, and this has helped maintain the novelty of our discoveries. Bright, keen students are especially welcome in our team, because students bring fresh eyes to the questions we explore. Particularly surprising and exciting, is our recent report of a previously unknown biological process, we term ‘cell-projection pumping’ (CPP). In CPP, cellular cytoplasm is injected into adjacent cells, Although discovering this in context of cancer, we think CPP may play help instruct stem cell differentiation and viral infection. From this, CPP has implications for cancer diagnosis, cancer chemotherapy, cancer immunotherapy, tissue regeneration and virology. We are looking for students to join the team, and help progress this exciting raft of projects.

I originally trained in Dentistry, and after a few years of general dental practice, concentrated on full time research from 1986, studying the microvasculature in chronic periodontitis. This was followed by three years of post-doctoral work in the Dept of Medicine at Royal Melbourne Hospital, Melbourne University. A two year post-doctoral research fellowship in Physiology, gave me the freedom to pursue any line of study that interested me, and was wonderful preparation to return to Sydney University as an independent academic. I have also had training in Oral Pathology, in context of my university appointment. In addition, I have benefited by one and a half years as a research fellow in Cell Biology at the Memorial Sloan Kettering Cancer Centre in New York. From this, I have been engaged full time academic research for over 30 years, and have developed experience across a wide range of laboratory and analytical methods. These include: cell culture; explant culture; small and large animal experimentation; light microscopy; confocal microscopy; fluorescence microscopy; time-lapse microscopy; transmission electron microscopy; scanning electron microscopy; atomic force microscopy; immuno-histochemistry; histochemistry; ELISA; bio-assays; protein chemistry; Western, Southern and Northern Blotting; molecular modelling; molecular biology; FACS analysis and cell isolation; single-cell tracking; finite element analysis; mathematical modelling; computer simulation; and relevant statistics. We often develop new methods, or adapt established protocols, to solve discrete experimental problems, and we encourage students to gain experience in this empowering skill during PhD training. Supervision of research students enrolled for: BSc Honours (6 students); MSc Dent (1 student); PhD (14 students); MDSc/DClinDent (12 students). Two honours students were awarded the University medal.

Discoveries of Note:
High endothelial venule phenotype is independent of lymphocyte emigration (J Pathol 1989,159:301). The vasculature expands during chronic inflammation in human chronic inflammation (J Oral Pathol Med 1991, 20:433; Microsc Res Tech 2002, 56:15).
Vascular basement membrane derived hyaline material in periodontal disease, potentially contributes to burst progression in periodontitis (J Oral Pathol Med 1989; 18:333; Med Hypotheses 1991, 1591 36:345; Microsc Res Tech 2002, 56: 15). Immunoglobulin derived amyloid deposits form in chronic periodontitis (J Oral Pathol Med 1994, 23:354; J Oral Pathol Med 1994, 23:358). G-CSF and GM-CSF are synthesised in a regulated manner by human vascular smooth muscle cells (Blood 1992, 80:2805; Atherosclerosis 1993, 99:241). Canalicular fragmentation is as an anti-embolic mechanism for apoptotic endothelium, associated with maintained anti-thrombotic fibrinolytic and platelet anti-aggregatory activity (Endothelium 1996, 4:177; Thromb Res 1998, 91:209; Thromb Haemost 2001, 85:915; Thromb Haemost 2002, 88:883; J Vasc Res 2005, 42:377)An anti-apoptotic activity of serum albumin for endothelium is mediated by a G-protein coupled endothelial receptor binding of a cryptic albumin protein domain, exposed by either intra-molecular movement or fragmentation of albumin. Albumin fragmentation maintains high vascularity early in wound healing. This work defines a novel drug target against hypertension, diabetes, and atherosclerosis, (J Cell Sci 1996, 109:2571; Microvasc Res 1999, 57:162; Proceedings of the Biological Mechanisms of Tooth Movement and Craniofacial Adaptation 2000, 49; Biochem Biophys Res Commun 2001, 284:83; Proceedings of the Biological Mechanisms of Tooth Eruption, 2006, 133-42; Cellular and Molecular Biology Letters 2009, 14:575; Wound Repair and Regeneration 2010 , 18:211).A previously unknown pattern of wound healing, ‘Adipogenic wound healing', where adipose as opposed to scar tissue forms (Proceedings of the Proceedings for the 7th World Congress for Microcirculation 2001 Sydney, 271-6; Anat Rec 2002, 267:28; Proceedings of the Biological Mechanisms of Tooth Movement and Craniofacial Adaptation 2004, 25-9).Based on incongruity between the clinical observation that there are few blood vessels in cancers, and the separate acceptance that cancers are angiogenic, we explored the possibility that cancer cells induce apoptosis in endothelium in a contact dependent manner. We confirmed this suspicion in co-culture experiments, and this formed the basis for ongoing work that led to our recent discovery of cell-projection pumping (J Pathol 2003, 201:395).Oral submucous fibrosis is disease of aberrant tissue remodelling, and we have defined some aspects of the biology of this disease as well as an effective physiotherapy for the condition (J Oral Pathol Oral Med 2009, 38:220; J Oral Pathol Oral Med 2010, 39:465; J Oral Pathol Oral Med 2014, 43:761; J Oral Pathol Oral Med 2015, 44: 591; Neuropathology of Drug Addictions and Substance Misuse. Vol. 3 Prescription Medications, Caffeine, Polydrug Misuse, and non-Drug Addictions. Editor: Professor Victor R Preedy. Elsevier, Academic Press, London. 2016, 785-792)Tooth eruption, bone remodelling and cyst expansion explained by bone remodelling mediated by strain sensing by soft-tissues closely applied to relevant bony surfaces (Arch Oral Biol, 2012, 57:1070; PLoS One. 2013, 8(3): e58803 Pages 1-18; Arch Oral Biology 2019, 98:1)Cell-Projection Pumping (CPP) is a novel mechanism for exchange of cytoplasm between mammalian cells, that dramatically changes the phenotype of receptor cells (J Pathol 2012, 228:495; Cytokine 2013, 62:48; PLoS One 2014, 9(6):e101202. Pages 1-7; PLoS One. 2019. 14(11):e0224800; . Biophysical Journal, 2020, 118: 1-13

Our laboratory (The Cellular and Molecular Pathology Research Unit) is based at Westmead Hospital in the Westmead Centre for Oral Health. It is well appointed for general laboratory procedures, and neighbours the School's Biomechanics laboratories as well as the Institute of Dental Research, providing access to further high quality laboratory facilities. Access to specialist equipment and expertise is via a network of collaborating laboratories throughout the Westmead and Camperdown campus. Notably, the Westmead Campus, including: the Westmead Institute of Medical Research; The Institute of Clinical Pathology and Medical Research; the Children's Hospital Westmead; and Children's Medical Research Institute, is a scientifically rich and stimulating environment that provides ample opportunity for collaboration and expert advice.

Selected publications

Zoellner H, Paknejad N, Cornwell J, Chami B, Romin Y, Boyko V, Fujisawa S, Kelly E, Lynch GW, Rogers G, Manova K, Moore MAS. A potential hydrodynamic mechanism for cytoplasmic transfer between mammalian cells: Cell-projection pumping. Biophysical Journal, 2020, 118: 1248-1260

Zoellner H, Chami B, Kelly E, Moore MAS. Increased cell size, structural complexity and migration of cancer cells acquiring fibroblast organelles by cell-projection pumping. PLoS One. 2019. 14(11):e0224800. https://doi.org/10.1371/journal.pone.0224800.

Sarrafpour B, Charbel EB, Li Q, Zoellner H. Roles of functional strain and capsule compression on mandibular cyst expansion and cortication. Archives of Oral Biology. 2019. 98:1-8

Sarrafpour B, Boughton P, Farahani RM, Cox SC, Denyer G, Kelly E, Zoellner H. A method for investigating the cellular response to cyclic tension or compression in three-dimensional culture. J of the Mechanical Behavior of Biomedical Materials. 2018. 88: 11-17.

Zoellner H, Paknejad N, Manova K, Moore MAS. A novel cell-stiffness-fingerprinting analysis by scanning atomic force microscopy: Comparison of fibroblasts and diverse cancer cell lines. 2015, Histochemistry and Cell Biology. DOI 10.1007/s00418-015-1363. 2015, 144:533-542.

David MS, Kelly E, Zoellner H. Opposite cytokine synthesis by fibroblasts in contact co-culture with osteosarcoma cells compared with transwell co-cultures. Cytokine. 2013, 62:48-51

Sarrafpour B, Swain M, Li Q, Zoellner H. Tooth eruption results from bone remodelling driven by bite forces sensed by soft tissue dental follicles: A finite element analysis. PLoS One. 2013, 8(3): e58803 Pages 1-18. doi:10.1371/journal.pone.0058803

David MS, Huynh MD, Kelly E, Rizos H, Coleman H, Rogers G, Zoellner H. Membrane and cytoplasmic marker exchange between malignant neoplastic cells and fibroblasts via intermittent contact: Increased tumour cell diversity independent of genetic change J Pathology. 2012, 228:495-505 

Bolitho C, Xaymardan M, Lynch G, Zoellner H. Vascularity during wound maturation correlates with fragmentation of serum albumin but not ceruloplasmin, transferrin, or haptoglobin. Wound Repair and Regeneration 2010 18:211-222

Zoellner H, Hofler M, Beckmann R, Hufnagl P, Vanyek E, Bielek E, Wojta J, Fabry A, Lockie S, Binder BR. Serum albumin is a specific inhibitor of apoptosis in human endothelial cells. J Cell Sci 1996;109(Pt 10):2571-80.