Associate Professor Lata Vadlamudi

Principal Research Fellow

UQ Centre for Clinical Research
Faculty of Medicine

Overview

Associate Professor Lata Vadlamudi is a Senior Staff Specialist in Neurology at the Royal Brisbane and Women’s Hospital; Epileptologist within the Comprehensive Epilepsy Program; Metro North Clinician Research Fellow; and Neurosciences Theme Leader at the University of Queensland Centre for Clinical Research. She is a Group Leader at UQCCR and her research group is entitled Epilepsy Research- Precision-based management. Webpage- https://clinical-research.centre.uq.edu.au/vadlamudi-group

She obtained her medical degree from the University of QLD and completed physician training in the field of Neurology. Further specialized training in epilepsy was undertaken in Melbourne, Sydney and the Mayo Clinic, USA. PhD was obtained from the University of Melbourne, which was entitled “The Genetics of Epilepsy: The Testimony of Twins”.

Clinical interests include integrating genomics into clinical care and management of women with epilepsy, in particular during pregnancy. Current research projects include developing patient-specific organoid models to personalise epilepsy care and a current MRFF-funded stem cell therapies PERSIST mission; RNA therapeutics; genomic and epigenomic studies in epilepsy, with a particular interest in twin studies.

Awards have included Metro North Clinician Research Fellowship; Highly Commended Clinical Research Award by Metro North Hospital and Health Service, Epilepsy Queensland Health Award for contributions to the medical care of people with epilepsy; and Leonard Cox Award from the Australian and New Zealand Association of Neurologists for outstanding contribution to research in the field of Neurology

Research Interests

  • Epilepsy genomics
    The goal is to demonstrate that integration of genomics into the clinical care of refractory epilepsy patients will significantly improve their healthcare and show that this can be delivered using available resources effectively and efficiently. This project involves the creation of a diagnostic genomic testing pathway for known genes associated with epilepsy. The mission will be accomplished by creating a diagnostic algorithm which incorporates accessible genomic testing for the treating neurologist, a multi-disciplinary approach for report generation, enabling a clinically meaningful report to the neurologists as well as individualised reports to patients. This process is supported by a genetic counsellor working with the research team and treating neurologists. By better understanding the cause of epilepsy, a more precision-based approach to treatment can be achieved.
  • RNA Therapeutics
    Our research focus is to move from symptomatic treatment for patients, which occurs in a reactive fashion, to a more proactive treatment approach of developing innovative therapeutic strategies based on the underlying pathology. RNA therapeutics, such as miRNAs in epilepsy, hold great promise for better understanding the cause and for the development of novel drug targets to improve the outcome of this debilitating disorder. This research will be in collaboration with the Centre for RNA in Neuroscience- Queensland Brain Institute, working to develop new RNA based therapeutic interventions for neurological disorders.
  • Patient-specific, in vitro brain organoid models
    Currently, finding the right medication can involve lengthy trials of sequential anti-seizure medications to get the most effective outcome for patients. Through the creation of a patient-specific (in vitro) epilepsy model and drug-screening platform, we can facilitate a new era of personalised, precision-based drug selection. This novel approach has the potential to change the current trial and error approach to get the right medication for patients more quickly. We have established resources to enable functional studies of identified variants; potential for gene-editing capabilities; and pharmacogenomic studies. Hence, this project has great potential to improve clinical outcomes from this debilitating disorder.
  • Epigenomics
    Epigenomics is the study of changes in gene expression without changes to the DNA sequence. Twins studies are an ideal paradigm to help differentiate between the three major components of phenotypic variation: genetics, shared, and non-shared environment. The discordant monozygotic twin model provides an elegant study design that controls for shared genetic and environmental factors, enabling a greater focus on the non-shared environment

Research Impacts

Our research is focused on better answering the two most common questions patients ask their neurologist in the Epilepsy Clinic What is the cause of my epilepsyand How can my epilepsy be treated?” A better understanding of the cause for an individual patient, will underpin the era of more personalised treatments to improve outcomes for this debilitating disorder.

1 in 26 people will develop epilepsy and the current “one size fits all model” is not effective for more than one third of patients who remain drug resistant (refractory epilepsy).

“What is the cause of my epilepsy”

The role of genomics has been well established in epilepsy, initially with family and twin studies and then with the discovery of single genes causing epilepsy. What has evolved is that the vast majority of epilepsy patients have a more complex genomic basis for their epilepsy.

Integrating genomic testing into clinical care

Genomics enables us to provide a better understanding of the cause of epilepsy for a particular patient. This approach will end the diagnostic odyssey of searching for how and why they developed epilepsy and will enable precision-based, personalised treatment approaches based on the individual’s genomic results.

“How can my epilepsy be treated?”

In Vitro brain organoid drug screening platforms

To fundamentally change the way drug resistant epilepsy patients are being treated we are developing a patient-specific, in vitro brain organoid drug-screening platform that can identify effective anti-seizure drugs. We plan to test whether such in vitro identified drug regimens are “real-world” effective in treating epilepsy in a particular drug-resistant patient, highlighting a precision-based approach for optimal drug selection – reducing the burden on patients and their families.

RNA Therapeutics

RNA, once thought to simply be an intermediate step in the transition from DNA code to the proteome, is increasingly being recognised as a critical feature for information processing in the brain. This is due, in part, to the discovery that 98% of our genes do not code for protein but, instead generate a myriad of noncoding regulatory RNAs that function in a cell-type and state-dependent manner. Indeed, RNA metabolism has been shown to be involved in a variety of brain disorders, including epilepsy. In recent years, major advances in the field have demonstrated that RNA, as a therapeutic intervention, has the potential to reverse, correct or slow the progression of disease.

Qualifications

  • Graduate Certificate in Diagnostic Genomics, Queensland University of Technology
  • Doctor of Philosophy, University of Melbourne
  • Fellow, Royal Australian College of Physicians
  • Fellow, Royal Australian College of General Practitioners
  • Bachelor of Medicine Bachelor of Surgery, The University of Queensland

Publications

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Supervision

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Available Projects

  • PERSIST, funded by the Medical Research Future Fund, is a new collaboration between the University of Queensland (QLD) and Monash University (VIC). We are now offering unique opportunities for trans-disciplinary honours/master/PhD research to students with background in neuroscience, cell biology, electrophysiology, machine learning, and clinical medicine. Students may be enrolled through either university, with opportunities to visit the other institution (depending on travel restrictions). Scholarships will be available for suitable students.

    Epilepsy affects 1 in 26 people. Patients with recurrent seizures that may cause injuries or even death. Despite the development of many new medications over the last 20 years, more than 30% of patients do not have their seizure controlled. Currently it is not possible to predict which medications, either singly or in combination, will be effective for an individual patient, and no patient can trial all possible combinations within their lifetime. Under the current paradigm, the patient is sequentially trialled on different medications, doses and combinations in the hope of eventually finding an effective regime. For the patient this protracted (often years long) journey results in substantive co-morbidity, loss of productivity and greater risk of sudden death.

    Instead of trial-and-error the PERSIST project will test a more personalised treatment strategy. The project aims to; a) use patient-specific induced pluripotent stem cell derived brain organoids to identify drugs that are able to modulate hyperactive neural activity, b) create an integrated predictive model for drug selection via artificial intelligence (AI) analysis of in vitro, clinical, and genomics data sets, c) validate treatment predictions in vitro and in real-world clinical care settings. The first part of this project will involve establishment of induced pluripotent stem cell lines from drug-resistant epilepsy patient blood samples and identify anti-seizure medications (ASMs) and drug combinations that suppress hyperactive neural activity in brain organoids derived from these cell lines. The second part of the project will involve integration of novel artificial intelligence approaches to further enhance the accuracy of these personalized drug efficacy profiles by incorporating single cell gene expression data sets, clinical information, and patient genomics data.

View all Available Projects

Publications

Journal Article

Conference Publication

  • Dibbens, L. M., Scheffer, I. E., Regan, B. M., Mandelstam, S., Crompton, D. E., Hodgson, B. L., Licchetta, L., Provini, F., Bisulli, F., Vadlamudi, L., Gecz, J., Connelly, A., Tinuper, P., Ricos, M. G., Berkovic, S. F. and Heron, S. E. (2014). Mutations in Depdc5 Are a Major Cause of Lesional and Non-Lesional Focal Epilepsy. 11th European Congress on Epileptology, Stockholm, Sweden, Jun 29-Jul 03, 2014. Hoboken, NJ, United States : Wiley-Blackwell Publishing. doi: 10.1111/epi.12675

  • Vadlamudi, L., Kjeldsen, N. J., Corey, L. A., Solaas, A. H., Friis, M. L., Pellock, J. M., Nakken, K. O., Milne, R. L., Scheffer, N. E., Harvey, S. A. and Berkovic, S. F. (2004). Is benign rolandic epilepsy genetically determined?. Annual Meeting of the American Epilepsy Society, New Orleans, LA, United States, 3-7 December 2004. Hoboken, NJ, United States: Wiley-Blackwell Publishing.

  • Vadlamudi, Lata , Somerville, Ernst , Neocleous, V., Mulley, John , Bertrand, D. and Berkovic, Samuel (2003). Do parasomnias and nocturnal frontal lobe epilepsy share the same molecular mechanisms? . Annual Meeting of the American Epilepsy Society, Boston, MA, United States, 5-10 December 2003.

  • Vadlamudi, Lata , Andermann, Eva , Lombroso, C. T., Schachter, S. C., Andermann, Fred and Berkovic, Samuel (2003). Epilepsy in Twins: Insights from unique historical data of William Lennox. Annual Meeting of the American Academy of Neurology, Honolulu, HI, United States, 29 March-5 April 2003.

  • Vadlamudi, Lata , Andermann, Eva , Lombroso, C. T. , Schachter, S. C., Roger Milne, John Hopper, Fred Andermann and Samuel Berkovic (2003). William Lennox’s twin studies compared with recent data: Lessons in classification and genetics. Annual Meeting of the American Epilepsy Society, Boston, MA, United States, 5-10 December 2003.

  • Vadlamudi, Lata , Parisi, John and Westmoreland, Barbara (2002). The EEG findings in Kufs disease. Annual Meeting of the Canadian Congress of Neurological Sciences, Vancouver, BC, Canada, 18-22 June 2002.

  • Vadlamudi, Lata , So, Elson , Worrell, Greg , Cascino, Greg and Lesnick, Tom (2001). Factors underlying scalp-EEG interictal epileptiform discharges in intractable frontal lobe epilepsy.. American Epilepsy Society, Philadelphia, PA, United Sates, 30 November-5 December 2001.

  • Vadlamudi, Lata , Galton, Clare , Jeavons, Susan , Tannenberg, Anthony and Boyle, Richard (1999). Rasmussens's Syndrome in a fifty-four year old female- More support for an adult variant. Meeting of the 23rd International Epilepsy Congress, Prague, Czech Republic, 12-17 September 1999.

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Associate Advisor

    Other advisors:

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • PERSIST, funded by the Medical Research Future Fund, is a new collaboration between the University of Queensland (QLD) and Monash University (VIC). We are now offering unique opportunities for trans-disciplinary honours/master/PhD research to students with background in neuroscience, cell biology, electrophysiology, machine learning, and clinical medicine. Students may be enrolled through either university, with opportunities to visit the other institution (depending on travel restrictions). Scholarships will be available for suitable students.

    Epilepsy affects 1 in 26 people. Patients with recurrent seizures that may cause injuries or even death. Despite the development of many new medications over the last 20 years, more than 30% of patients do not have their seizure controlled. Currently it is not possible to predict which medications, either singly or in combination, will be effective for an individual patient, and no patient can trial all possible combinations within their lifetime. Under the current paradigm, the patient is sequentially trialled on different medications, doses and combinations in the hope of eventually finding an effective regime. For the patient this protracted (often years long) journey results in substantive co-morbidity, loss of productivity and greater risk of sudden death.

    Instead of trial-and-error the PERSIST project will test a more personalised treatment strategy. The project aims to; a) use patient-specific induced pluripotent stem cell derived brain organoids to identify drugs that are able to modulate hyperactive neural activity, b) create an integrated predictive model for drug selection via artificial intelligence (AI) analysis of in vitro, clinical, and genomics data sets, c) validate treatment predictions in vitro and in real-world clinical care settings. The first part of this project will involve establishment of induced pluripotent stem cell lines from drug-resistant epilepsy patient blood samples and identify anti-seizure medications (ASMs) and drug combinations that suppress hyperactive neural activity in brain organoids derived from these cell lines. The second part of the project will involve integration of novel artificial intelligence approaches to further enhance the accuracy of these personalized drug efficacy profiles by incorporating single cell gene expression data sets, clinical information, and patient genomics data.