Michael A Cahill

Honorary: Australian National University. Adjunct: Charles Sturt University. Advisor: Cognition Therapeutics.

Citation: Thejer, B.M.; Infantino, V.; Santarsiero, A.; Pappalardo, I.; Abatematteo, F.S.; Teakel, S.; Van Oosterum, A.; Mach, R.H.; Denora, N.; Lee, B.C.; et al. Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97. Int. Abstract: Sigma-2 receptor (S2R) is a S2R ligand-binding site historically associated with reportedly 2...

Maintaining student engagement in online and recorded lectures is a challenging aspect of higher education. In light of this, active learning through in-lecture question activities was investigated using a pre-teaching focus group (n = 12) and student evaluations (n = 43) after an in-class trial. Data analysis was underpinned by flow theory, which...

The title usage of Unde venisti ‘from where have you come’ is from a now dead language (Latin) that foundationally influenced modern English (not the major influence, but an essential formative one). This is an apt analogy for how both the ancient eukaryotic and eumetazoan functions of PGRMC proteins (PGRMC1 and PGRMC2 in mammals) probably influenc...

The title usage of Latin Quo vadis ‘where are you going’ extends the question Unde venisti from where ‘did you come?’ posed in the accompanying paper and extends consideration of how ancient eukaryotic and eumetazoan functions of progesterone receptor membrane component (PGRMC) proteins (PGRMC1 and PGRMC2 in mammals) could influence modern human he...

We recently reported that the membrane associated progesterone receptor (MAPR) protein family (mammalian members: PGRMC1, PGRMC2, NEUFC and NENF) originated from a new class of prokaryotic cytochrome b5 (cytb5) domain proteins, called cytb5M (MAPR‐like). Relative to classical cytb5 proteins, MAPR and ctyb5M proteins shared unique sequence elements...

We recently reported that the membrane associated progesterone receptor (MAPR) protein family (mammalian members: PGRMC1, PGRMC2, NEUFC and NENF) originated from a new class of prokaryotic cytochrome b5 (cytb5) domain proteins, called cytb5M (MAPR-like). Relative to classical cytb5 proteins, MAPR and ctyb5M proteins shared unique sequence elements...

The multiple functions of PGRMC1, the archetypal heme-binding eukaryotic MAPR family member, include steroidogenic regulation, membrane trafficking, and steroid responsiveness. The interrelationships between these functions are currently poorly understood. Previous work has shown that different MAPR subclasses were present early in eukaryotic evolu...

In previous studies, we reported that progesterone receptor membrane component 1 (PGRMC1) is implicated in progestin signaling and possibly associated with increased breast cancer risk upon combined hormone replacement therapy. To gain mechanistic insight, we searched for potential PGRMC1 interaction partners upon progestin treatment by co-immunopr...

This is a preface by the guest editors of the special issue of Cancers featuring the biology of progesterone (P4) receptor membrane component (PGRMC) proteins as it relates to metabolism and cancer [...]

The σ-2 receptor (S2R) complex has been implicated in CNS disorders ranging from anxiety and depression to neurodegenerative disorders such as Alzheimer's disease (AD). The proteins comprising the S2R complex impact processes including autophagy, cholesterol synthesis, progesterone signaling, lipid membrane-bound protein trafficking, and receptor s...

Background: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Results: Here, we show that...

Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results: We demonstrate that manipulating PGRMC1 phosphory...

The membrane-associated progesterone receptor (MAPR) family consists of heme-binding proteins containing a cytochrome b5 (cytb5) domain characterized by the presence of a MAPR-specific interhelical insert region (MIHIR) between helices 3 and 4 of the canonical cytb5-domain fold. Animals possess three MAPR genes (PGRMC-like, Neuferricin and Neudesin...

Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results: We demonstrate that manipulating PGRMC1 phosphorylat...

Background: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Results: Here, we show that mut...

Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results: We demonstrate that manipulating PGRMC1 phosphorylat...

Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results: We demonstrate that manipulating PGRMC1 phosphorylat...

PGRMC1 is a protein from the MAPR family with a range of cellular functions. PGRMC1 has been described to play a role in fertility, neuroprotection, steroidogenesis, membrane trafficking and in cancer cell biology. PGRMC1 represents a likely key regulator of cell metabolism and proliferation, as well as a potential target for anti-cancer therapies....

Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Here, we show that mutagenic manipulation o...

Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Here, we demonstrate that manipulating PGRMC1 phosphorylation status in M...

Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Here, we show that mutagenic manipulation o...

Background The membrane-associated progesterone receptor (MAPR) family consists of heme-binding proteins containing a cytochrome b 5 (cytb 5 ) domain characterized by the presence of a MAPR-specific interhelical insert region (MIHIR) between helices 3 and 4 of the canonical cytb5-domain fold. Animals possess three MAPR families (PGRMC-like, Neuferr...

Background: The cytomorphological features in the distinction between phyllodes tumour (PT) and fibroadenoma (FA) on fine needle aspiration biopsy (FNAB) remains challenging because of the biphasic nature of these lesions and the rarity of PT. Methods: FNAB smears of histologically confirmed PT (N = 26) and FA (N = 78) cases were retrieved from...

A complex PGRMC1-centred regulatory system controls multiple cell functions. Although PGRMC1 is phosphorylated at several positions, we do not understand the mechanisms regulating its function. PGRMC1 is the archetypal member of the membrane associated progesterone receptor (MAPR) family. Phylogentic comparison of MAPR proteins suggests that the an...

Progesterone Receptor Membrane Component 1 (PGRMC1) is located in many different subcellular locations with many different attested and probably location-specific functions. PGRMC1 was recently identified in the mitochondrial outer membrane where it interacts with ferrochelatase, the last enzyme in the heme synthetic pathway. It has been proposed t...

// Michael A. Cahill 1 , Jalal A. Jazayeri 1 , Zaklina Kovacevic 2 and Des R. Richardson 2 1 School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia 2 Molecular Pharmacology and Pathology Program, Department of Pathology, Bosch Institute, University of Sydney, Sydney, NSW, Australia Correspondence to: Michael A. Cahill,...

Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous fluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from imaging of nat...

Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous autofluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from autofluore...

Hyperspectral imaging based on endogenous contrast provides a new non-invasive method to characterise cells and tissues. Cellular content and maps of native fluorophores help monitor biological processes, with proper account of intrinsic cellular heterogeneity.

Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible...

Measurement of endogenous free and bound NAD(P)H relative concentrations in living cells is a useful method for monitoring aspects of cellular metabolism, because the NADH∕NADþ reduction-oxidation pair is crucial for electron transfer through the mitochondrial electron transport chain. Variations of free and bound NAD(P)H ratio are also implicated...

The WHI trial suggests an increase of breast cancer in postmenopausal women probably according to the progestogenic compound, i.e. medroxyprogesterone acetate (MPA). However, the mechanism for a possible carcinogenic effect of MPA remains unclear so far. Progesterone receptor membrane component-1 (PGRMC1) may be important in tumorigenesis and thus...

Clinical trials have demonstrated an increased risk of breast cancer during estrogen/norethisterone (NET) therapy. With this in mind, the effects of estrogen/NET combination on the proliferation of breast cancer cells overexpressing the progesterone receptor membrane component 1 (PGRMC1) were examined. The same combination was used for the first ti...

Objectives: Dienogest (DNG) is already used in hormone therapy, since recently being also the progestogenic component of the first estradiol based contraceptive pill. Data on breast cancer risk are currently not available. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in tissues of breast cancer patients and has already b...

Paradise Rediscovered. Were Europe's first farmers ruled by an elite aristocracy who passed themselves off as "gods", commanding secret knowledge that included ambrosia that extended their life spans? My first book published by Glass House Books, Brisbane is published as two paperback (PB) volumes or a single volume eBook. ISBN 9781921869488 (Vol 1...

Objectives: Recently the first monophasic contraceptive pill containing estradiol has been developed which is thought to be a milestone in contraception. Nomegestrol acetate (NOM) is the progestogenic component. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in the tissue of breast cancer patients, and can predict a proges...

Objectives: Evidence is accumulating that progestogens may play a crucial role in the development of breast cancer under contraception and hormone therapy in reproductive and menopausal women. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. T...

Fragestellung: Gestagene scheinen eine entscheidende Rolle bei der Entstehung eines Mammakarzinoms in Bezug auf die Empfangnisverhutung und die Hormontherapie in der Postmenopause zu spielen. Die Progesteronrezeptor-Membrankomponente 1 (PGRMC1), die in Mammakarzinom-Zellen exprimiert ist, konnte fur die Tumorgenese wichtig sein und somit das Brustk...

Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project...

Progestogens influence mammary gland development and probably breast cancer tumorigenesis by regulating a broad spectrum of physiological processes. We investigated receptor membrane-initiated actions of progestogens in MCF-7 breast cancer cells overexpressing progesterone receptor membrane component 1 (PGRMC1). MCF-7 cells were stably transfected...

Human group IIA-secreted phospholipase A2 (sPLA2-IIA) is an important regulator of cytokine-mediated inflammatory responses in both in vitro and in vivo models of rheumatoid arthritis (RA). However, treatment of RA patients with sPLA2-IIA inhibitors shows only transient benefit. Using an activity-impaired sPLA2-IIA mutant protein (H48Q), we show th...

The present invention relates to the use of an active ingredient and to a method for the prevention or treatment of tumors, the diagnostic detection of disorders associated with these tumors, and pharmaceutical compositions and kits related thereto.

Progesterone influences mammary gland development and probably breast cancer tumorigenesis and functions by regulating a broad spectrum of physiological processes. We investigated receptor membrane-initiated actions of progesterone in MCF-7 breast cancer cells via progesterone receptor membrane component 1 (PGRMC1). The expression of PGRMC1 in brea...

Following the publication of our article [1] we noticed an error in the abstract, within the paragraph headed 'Results'. The serine residue, serine-181, referred to in this paragraph should be serine-180. The paragraph should therefore read as follows: Proteins significantly differentially abundant between estro-gen receptor negative and estrogen r...

2D-PAGE remains a widely employed proteomics method because it provides the highest separating resolution of intact polypeptide isoforms that are amenable to subsequent characterization (1, 2). ProteoTope is a differential radioactive detection method that we developed based upon temporally separated exposures of iodinated proteins on 2D-PAGE gels...

It has long been apparent that the separation capacity of conventional 18 cm IPGs as the first separation step in two dimensional polyacrylamide gel electro-phoresis (2D-PAGE) was theoretically incapable of separating the complexity that is to be expected by the protein species of a mammalian cell line or tissue (1). We first attempted to improve t...

To identify pretherapeutic predictive biomarkers in tumor biopsies of patients with locally advanced esophageal adenocarcinomas treated with neoadjuvant chemotherapy, we used an explorative proteomic approach to correlate pretherapeutic protein expression profiles with tumor response to neoadjuvant chemotherapy. Thirty-four patients with locally ad...

Breast tumors lacking the estrogen receptor-alpha (ER-alpha) have increased incidence of resistance to therapy and poorer clinical prognosis. Whole tissue sections from 16 cryopreserved breast cancer tumors that were either positive or negative for the ER (eight ER positive and eight ER negative) were differentially analyzed by multiplex imaging of...

Supplementary materials. Presented are Supplementary discussions entitled 'Validation of the differential abundance profile' and 'Candidate PGRMC1 interacting proteins'. It additionally contains two supplementary tables: Table S1 ('Protein spots that contained multiple identifications of individual proteins as gene products') and Table S2 ('Clinica...

Die Progesteronrezeptor-Membrankomponente 1 (PGRMC1) ist ein 28kDa Protein, das zur „membrane-associated progesterone receptor“ (MAPR) Proteinfamilie gehort. Wir konnten zeigen, dass PGRMC1 im ER-negativen Mammakarzinom hochreguliert und phosphoryliert ist. Ziel dieser Studie war die weitergehende Charakterisierung des PGRMC1 beim Mammakarzinom. PG...

Besides the mitogenic action of estrogens in breast cancer cells there is also evidence that estrogen receptors mediate protective, anti-invasive effects. The aim of this project was to identify downstream ER-dependent proteins differentially expressed in fresh-frozen ER-positive and –negative breast cancer. Tissue sections from eight ER-positive a...

Living mice were subjected to whole body labeling by intravenous infusion of [(13)C]glucose as the sole carbon source. After 10 h infusion the mice were sacrificed, and liver proteins were separated by two-dimensional polyacrylamide gel electrophoresis. Five spots were found to contain mitochondrial aldehyde dehydrogenase (ALDH2) by matrix assisted...

Progesterone receptor membrane component 1 (PGRMC1) contains a cytochrome b5 domain fold and belongs to the so-called membrane-associated progesterone receptor (MAPR) protein family that is widespread in eukaryotes. PGRMC1 and the related PGRMC2 mammalian family member diverged sometime after the evolution of segmented metazoan body plan and the ap...

Breast cancer is one of the most common cancers observed in women in industrialized Western countries. The development of novel diagnostic methods and the application of modern systemic therapies have significantly optimized early detection and therapy of breast cancer. However, many patients are currently overtreated. Traditionally, tumours have b...