Personal profile

Overview

In the past 12 years my research has focused on investigating novel mechanisms and therapies for cardiac hypertrophy and heart failure in animal models. As a pharmacist I have a special interest in the translation of my findings into human drug therapy for heart disease and I wish to focus my career on contributing to the fascinating and decisive early steps in the long process of drug development.

For more details please see article: European Perspectives in Cardiology, Young Investigator Spotlight (Circulation, Journal of the American Heart Association)

2001-2003 Masters studies in Egypt: Using advanced biochemical and electron microscopic methods I investigated the role of TNF-α inhibition and antioxidants in protection against doxorubicin-induced cardiomyopathy in rats. My Masters study resulted in 2 publications (Mohamed et al., J Pharm. Pharmacol., 2004 & Mohamed et al., Egy. J. Biochem. Mol. Biol. 2005) which described combination of TNF-α inhibition and antioxidant therapy could protect against the cardiac side effects of this powerful cancer chemotherapy.


2005-2008 PhD studies in Manchester: As a PhD student in the Cardiovascular Medicine research group I continued investigating novel and potentially ‘druggable’ proteins that regulate cardiac hypertrophy and heart failure. In 2005, one of the proteins with unknown function in the heart was the plasma membrane calcium ATPase pump isoform 4 (PMCA4) which pumps calcium out of the heart cell, but does not contribute to contraction/relaxation. Therefore, I decided to explore its role using transgenic and knock-out mouse models, and cellular models and was able to describe a novel role for PMCA4 in regulating cardiac contractility indirectly through modulation of neuronal nitric oxide synthase (nNOS). This work resulted in three publications in highly recognized journals (Williams et al., JBC 2006, Mohamed et al., JBC 2009 and Oceandy et al., Circulation 2009), and several oral and poster presentations at international cardiovascular conferences. 


2008-2011 Post Doctoral training in Manchester: In my first post-doctoral position I expanded my interest from pure molecular biology to live imaging of subcellular compartments, one of the most fascinating developments in modern heart research. To this end, I trained for several months with Prof. M. Zaccolo at the University of Glasgow and started a collaboration with Prof. Michael I. Kotlikoff (Cornell University, USA). Through these collaborations I have developed new tools to assess the changes in local calcium, cAMP and cGMP to explore the role of PMCA4 in modulating compartmentalized cardiac signalling during cardiac hypertrophy and failure. This is carried out using live cell bio-imaging fluorescence resonance emission transfer (FRET) techniques. I independently transferred this complex technology to Manchester (Bio-imaging Facility, Smith Building). Using these methods I first described a locally confined cAMP, cGMP and calcium space in the vicinity of PMCA4 in myocardial caveolae. My postdoctoral work has been highly recognized. I was awarded one of the three Young Investigator Awards (Basic Science) at the European Society of Cardiology Congress in 2010, the largest cardiology conference in the world. In addition, an extensive interview with me was published in Circulation, the leading international cardiovascular journal (European Perspectives in Cardiology. Circulation. 2010; 122(10):f55-60). Several publications will arise from this work; two have been published (Mohamed et al. Methods Mol Biol. 2010;637: 333-42 and Mohamed et al., JBC 2011).

2012-ongoing: (See Research Section below)


 

Biography

- Honorary Lecturer. Cardiovascular Research Institute, Faculty of Medical and Human Sciences, University of Manchester (July 2015 ongoing)

- Research Fellow. J David Gladstone Research Institutes (Cardiovascular), University of California – San Francisco (December 2013 ongoing

- Research Fellow. Cardiovascular Research institute, Faculty of Medical and Human Sciences, University of Manchester (August 2013 - June 2015)

- Visiting Lecturer. Dept. Biochemistry, Faculty of Pharmacy, Zagazig University, Egypt (August 2008 ongoing)

- Post Doctoral Research Associate. Cardiovascular Research institute, Faculty of Medical and Human Sciences, University of Manchester (October 2008- July 2013)

- International Research Fellow. University of Gottingen, Germany (April-July 2012) In Prof. Gerd Hasenfuss and Dr. Kaomei Guan’s laboratory for specialised training on human stem cells and induced pluripotent stem cells and their differentiation into cardiomyocytes.

- Visitor Research Fellow. European screening port, Hamburg, Germany (August 2011) for specialised training on high throughput drug screening.

- Visitor Research Fellow. Glasgow, UK (June 2007) In Prof. Manuela Zaccolo laboratory for specialised training on compartmentalised imaging of cAMP, cGMP and calcium.

- PhD student. Cardiovascular Medicine, Faculty of Medical and Human Sciences, University of Manchester (April 2005- May 2008) In Prof. Ludwig Neyses’ lab. Thesis entitled “Identification of the molecular mechanisms by which plasma membrane calcium ATPase isoforms 1 and 4 regulate cardiac signalling”

- Part time teaching assistant. Faculty of Life Sciences, University of Manchester (September 2006 - August 2008)

- Assistant Lecturer. Dept. Biochemistry, Faculty of Pharmacy, Zagazig University, Egypt (April 2003 - April 2005)

- Demonstrator. Dept. Biochemistry, Faculty of Pharmacy, Zagazig University, Egypt (March 2001 - March 2003)

- Pharmacist in military clinics in Egypt. (2000-2001 as a part of obligatory military service).
 

Research interests

To pursue my long-term goal of translating my findings in mouse models into human drug therapy for heart failure (at least with regard to the initial steps), I have taken further steps in three main directions:

  1. I have developed a medium throughput screening assay for PMCA4 activity to screen for specific inhibitors (Mohamed et al., Methods Mol Biol, 2010) and in collaboration with the European Screening Port (Hamburg) I have established a novel fluorescent-based high throughput screening assay for PMCA4 activity to screen for more specific inhibitors (Mohamed et al., J Pharmacy & Pharmaceutical Sciences, 2013). This work resulted in a Bill Gates grant award phase I ($100,000; 2.5% success rate).
  2. Several heart failure treatments developed on the basis of mouse experiments have failed in humans and therefore the transition from a mouse to a human system is by no means trivial but is a key step for future drug development. In addition, the lack of human cardiac tissue (or a suitable human cardiac cell line) is a severely limiting factor in translating the basic research findings in animal models into human applicable treatments. Therefore, I have decided to move into the field of human induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) which is the first human relevant cardiac cell model with the additional potential to derive patient-specific cardiac cells. I spent some time (April – July 2012) in Prof. Gerd Hasenfuss and Dr. Kaomie Guan’s lab (Gottingen, Germany) and learnt how to generate human iPS-CM. To support this training I was awarded the international scholar training fellowship from the NHS Biomedical Research Centre (£8000). As a first success, in December 2012 I was awarded CRACK IT Challenge 10 (PreDART Phase I) funding from the NC3Rs (£100,000) for prediction of human developmental and reproductive toxicity through non-mammalian assays.
  3. To further progress my career, on August 2013 I was awarded the University of Manchester travel fellowship for further training on the cutting edge direct cardiac reprogramming technologies in addition to the single cell genome and epigenome profiling during the reprogramming process in Prof. Deepak Srivastava laboratory at the J David Gladstone Research institutes. During this training I was able to further progress my starting up projects and learn the essential technologies which I will need to run my laboratory. During this training, I was able to lay the groundwork for the proposed research by developing a novel screening platform for direct cardiac reprogramming and to run a high-throughput small molecule screening to improve the efficiency of direct cardiac reprogramming. I was able to identify small molecules (mainly TGF-β and WNT inhibitors) which are able to enhance the efficiency of cardiac reprogramming by 7 folds. Currently I aim to investigate the molecular mechanisms by which TGF-β and WNT signaling control the direct reprogramming process and perform the first translational attempt to use the small molecules to enhance in vivo cardiac reprogramming.
  4. As part of my interest in pharmaceutical application of my research: In collaboration with the NC3Rs the European Screening Port (Hamburg) we are developing novel methods to screen for cardiotoxicity and developmental defects using human pluripotent stem cells. This project has recently received funding from the NC3Rs for a proof of concept study for one year. For more details see: https://www.nc3rs.org.uk/using-human-pluripotent-stem-cell-derived-cardiomyocytes-test-drug-cardiac-toxicity-0

Teaching

PEP tutor for 1st year medical students (September 2012 ongoing).

Tutor for MRes in tissue regeneration students (September 2012 ongoing)

Part time teaching assistant (September 2006 - August 2008 Faculty of Life Sciences - University of Manchester - UK)
Run biochemistry practicals for undergraduate students.

Assistant Lecturer (April 2003 - April 2005 Biochemistry Dept. Faculty of Pharmacy, Zagazig University, Egypt)
While I was an assistant lecturer I was responsible about running biochemistry practicals for undergraduate students with full responsibility regarding the practical, as well as sharing in the research activities in the department.

Demonstrator (March 2001 - March 2003 Biochemistry Dept. Faculty of Pharmacy, Zagazig University, Egypt)

While I was a demonstrator I was responsible for running biochemistry practicals for undergraduate students under supervision

My collaborations

  • Prof. Ludwig Neyses University of Manchester & University of Luxemburg
  • Prof. Deepak Srivastava University of California San Francisco
  • Dr. Elizabeth Cartwright University of Manchester
  • Dr. Delvac Oceandy University of Manchester
  • Dr. Ming Lei University of Manchester
  • Dr. Sheraz Gul European screening port, Hamburg (Germany)
  • Prof. Sue Kimber University of Manchester
  • Dr. K Guan University of Goettingen (Germany)
  • Dr. Farid Khan University of Manchester
  • Prof. Manuela Zaccolo University of Glasgow
  • Dr. Timo Strunker Max Planck institute (Germany)
  • Prof. Micheal Kotlikoff Cornell University (USA)
  • Prof. Deepak Srivastava Gladstone Research Institutes (USA)
  • Prof. Bruce Conklin Gladstone Research Institutes (USA)
  • Prof. Bethany Pruitt Stanford University (USA)
  • Prof. Roberto Latini Mario Nigri Institute (Italy)

Memberships of committees and professional bodies

  • Member of the American Heart Association
  • Member of the British Cardiac Research Society
  • Member of the International Society of Heart Research
  • Member of the European heart failure association

Methodological knowledge

Stem cell research: Generation of lentivirus, generation of Induced plueripotent stem cells from fibroblasts and differentiation of stem cells into cardiomyocytes in addition to direct reprogramming of fibroblasts into cardiomyocytes.

Compartmentalised Live cell imaging using genetically modified flourescent probes to assess the spatially localised cAMP, cGMP and calcium in different cardiac cell compartments. 

Molecular biology techniques DNA cloning, recombinant adenovirus generation and purification, isolation of neonatal rat cardiomyocytes as well as adult mouse cardiomyocytes, determination of calcium transients in neonatal rat cardiomyocytes using Indo-1 calcium sensitive dye, live cell imaging using nitric oxide sensitive dye to determine the NO bioavalability in isolated cardiomyocytes, ATPase activity assay, Western blot, co-immunoprecipitation, PCR, radioactivity assays and ELISA assays.  

Biochemical techniques: to assess the oxidative stress and damage in heart tissue as well as in serum e.g. serum levels of creatine kinase and lactate dehydrogenase, TNF-alpha, nitric oxide levels and lipid profile (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol and free fatty acids). Left ventricular levels of superoxide anion, lipid peroxide, catalase, superoxide dismutase, total and non-protein-bound thiols were determined. In addition, I have used electron microscopy to investigate the levels of apoptosis in heart sections.

Qualifications

PhD study in Molecular Medicine (funded by the Egyptian Government):

April 2005-until May 2008 Faculty of Medical and Human Sciences, University of Manchester, UK
Successfully passed the viva 21st of May 2008

Master degree in Biochemistry

2001-2003 Faculty of Pharmacy, Zagazig University, Egypt

Bachelor of Pharmacy

1994-1999 Faculty of Pharmacy, Zagazig University, Egypt

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being
  • SDG 6 - Clean Water and Sanitation
  • SDG 17 - Partnerships for the Goals

Research Beacons, Institutes and Platforms

  • Manchester Regenerative Medicine Network

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