Associate Professor Lata Vadlamudi

Principal Research Fellow

UQ Centre for Clinical Research
Faculty of Medicine
l.vadlamudi@uq.edu.au
+61 7 334 65034

Overview

Associate Professor Lata Vadlamudi has been a researcher in the field of epilepsy since 2002 and has been a neurologist in clinical practice since 2000. Associate Professor Lata Vadlamudi is a senior Staff Specialist in Neurology at the Royal Brisbane and Women’s Hospital and Group Leader at the UQ Centre for Clinical Research.

Epilepsy is one of the most common neurological disorders affecting over 50 million people worldwide and is characterised by the occurrence of seizures. One in 26 people will develop epilepsy during their lifetime. Despite more than 20 anti-epileptic medications, more than 30% of patients are not able to control their seizures with anti-epileptic medications.

Current research interests include:

(1) Integrating genomics into clinical practice, in order to improve patient care and facilitate precision-based treatment choices.

(2) Functional genomic models in epilepsy

(3) Genomic and epigenomic landscapes of epilepsy, in order to expand our understanding of the cause of this complex disease.

Clinical Genomics

The goal is to demonstrate that the 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 screening for genes, to see if we can identify a cause for epilepsy.

The mission will be accomplished by creating a diagnostic and management algorithm that 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.

Functional Genomics

The rate of gene discovery, however, has outpaced our ability to understand the pathophysiology of gene variants and how they relate to phenotypes. There is an imperative need to develop high-throughput functional analyses, such as induced pluripotent stem cells and cerebral organoids (3D neuronal networks), that are able to model the combinatorial impact of genetic variants observed in patients and their functional impact. Further proof of principle approach would involve introducing some common genetic variants into a control pluripotent cell line, to determine which are of functional significance.

Epigenomics

Epigenetics is the study of changes in gene expression without changes to the DNA sequence. The most studied epigenetic mechanism is DNA methylation. Twins are an ideal paradigm for differentiating between the three major components of phenotypic variation: genetics, shared, and non-shared environment. The discordant monozygotic twin model further provides an elegant study design that controls for shared genetic and environmental factors, enabling focus on the non-shared environment, the largest component of risk variance across all chronic disorders. Twin models are ideal for understanding the epigenetic and genetic landscape in epilepsies.

Research Impacts

With the majority of epilepsy of presumed genetic aetiology and with one quarter of patient’s failing to respond to at least two anti-epileptic drugs, there is a critical need to expand understanding of the genomic and epigenomic landscapes of epilepsy, to improve treatment outcomes for this debilitating disorder.

This research is focused on answering two of the most difficult clinical questions that neurologists struggle to answer in the epilepsy clinic – “What is the cause of my epilepsy” and “How can my epilepsy be treated?”.

Epilepsy is one of the most common neurological disorders affecting over 50 million people worldwide. Epilepsy is characterised by the clinical symptom of seizures, which are due to neuronal network hyper-synchronization. One in 26 people will develop epilepsy during their lifetime. In the Global Burden of Disease 2010 study, severe epilepsy has an unacceptable burden, ranking fourth out of 220 health conditions in terms of disability weight. The economic impact is also substantive with high healthcare costs associated with epilepsy, with greater costs for uncontrolled epilepsy.

Despite more than 20 anti-epileptic drugs, more than 30% of patients are not able to control their seizures with anti-epileptic drugs. Only 35% of epilepsy cases have a clear extraneously-acquired cause, such as head injury or stroke and the vast majority of epilepsy cases have a genetic basis. The genomic component of epilepsies was clearly recognised in familial and twin studies prior to the genomic era. Next generation sequencing has led to over 1000 genes associated with epilepsy.

The rate of gene discovery however, has outpaced our ability to understand the pathophysiology of gene variants and if they can cause seizures. There is an imperative need to develop high-throughput functional analyses, such as induced pluripotent stem cells and cerebral organoids (3D neuronal networks), that are able to model the combinatorial impact of genetic variants observed in patients and their functional impact.

Controlling the number of seizures has the greatest impact on reducing the burden of epilepsy. The other major outcome is a diagnosis for the patient to end the “diagnostic odyssey” of repeated investigations and hospital visits searching for answers, which has an enormous negative impact on their journey. The health impacts that will arise are substantive in terms of patient and family quality of life.

With the rapid increase in gene discovery in epilepsy, functional genomics are required to understand the role of complex genomic landscapes within individual patients and provide patients with a cause for their epilepsy. The future lies in then developing bespoke treatments, based on the functional genomics outcomes, to ultimately cure this debilitating disorder.

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

  • Mohandas, Namitha, Loke, Yuk Jing, Mackenzie, Lisa, Bennett, Carmen, Berkovic, Samuel F., Craig, Jeffrey M. and Vadlamudi, Lata (2019). Deciphering the role of epigenetics in self-limited epilepsy with centrotemporal spikes. Epilepsy Research, 156 106163, 106163. doi: 10.1016/j.eplepsyres.2019.106163

  • Mohandas, Namitha, Loke, Yuk Jing, Hopkins, Stephanie, Mackenzie, Lisa, Bennett, Carmen, Berkovic, Samuel F., Vadlamudi, Lata and Craig, Jeffrey M. (2019). Evidence for type-specific DNA methylation patterns in epilepsy: a discordant monozygotic twin approach. Epigenomics, 11 (8) epi-2018-0136, 951-968. doi: 10.2217/epi-2018-0136

  • Zhang, Yue-Hua, Burgess, Rosemary, Malone, Jodie P., Glubb, Georgie C., Helbig, Katherine L., Vadlamudi, Lata, Kivity, Sara, Afawi, Zaid, Bleasel, Andrew, Grattan-Smith, Padraic, Grinton, Bronwyn E., Bellows, Susannah T., Vears, Danya F., Damiano, John A., Goldberg-Stern, Hadassa, Korczyn, Amos D., Dibbens, Leanne M., Ruzzo, Elizabeth K., Hildebrand, Michael S., Berkovic, Samuel F. and Scheffer, Ingrid E. (2017). Genetic epilepsy with febrile seizures plus: refining the spectrum. Neurology, 89 (12), 1210-1219. doi: 10.1212/WNL.0000000000004384

View all Publications

Publications

Journal Article

  • Mohandas, Namitha, Loke, Yuk Jing, Mackenzie, Lisa, Bennett, Carmen, Berkovic, Samuel F., Craig, Jeffrey M. and Vadlamudi, Lata (2019). Deciphering the role of epigenetics in self-limited epilepsy with centrotemporal spikes. Epilepsy Research, 156 106163, 106163. doi: 10.1016/j.eplepsyres.2019.106163

  • Mohandas, Namitha, Loke, Yuk Jing, Hopkins, Stephanie, Mackenzie, Lisa, Bennett, Carmen, Berkovic, Samuel F., Vadlamudi, Lata and Craig, Jeffrey M. (2019). Evidence for type-specific DNA methylation patterns in epilepsy: a discordant monozygotic twin approach. Epigenomics, 11 (8) epi-2018-0136, 951-968. doi: 10.2217/epi-2018-0136

  • Zhang, Yue-Hua, Burgess, Rosemary, Malone, Jodie P., Glubb, Georgie C., Helbig, Katherine L., Vadlamudi, Lata, Kivity, Sara, Afawi, Zaid, Bleasel, Andrew, Grattan-Smith, Padraic, Grinton, Bronwyn E., Bellows, Susannah T., Vears, Danya F., Damiano, John A., Goldberg-Stern, Hadassa, Korczyn, Amos D., Dibbens, Leanne M., Ruzzo, Elizabeth K., Hildebrand, Michael S., Berkovic, Samuel F. and Scheffer, Ingrid E. (2017). Genetic epilepsy with febrile seizures plus: refining the spectrum. Neurology, 89 (12), 1210-1219. doi: 10.1212/WNL.0000000000004384

  • Vadlamudi, Lata, Milne, Roger L., Lawrence, Kate, Heron, Sarah E., Eckhaus, Jazmin, Keay, Deborah, Connellan, Mary, Torn-Broers, Yvonne, Howell, R. Anne, Mulley, John C., Scheffer, Ingrid E., Dibbens, Leanne M., Hopper, John L. and Berkovic, Samuel F. (2014). Genetics of epilepsy: The testimony of twins in the molecular era. Neurology, 83 (12), 1042-1048. doi: 10.1212/WNL.0000000000000790

  • Scheffer, Ingrid E., Heron, Sarah E., Regan, Brigid M., Mandelstam, Simone, Crompton, Douglas E., Hodgson, Bree L., Licchetta, Laura, Provini, Federica, Bisulli, Francesca, Vadlamudi, Lata, Gecz, Jozef, Connelly, Alan, Tinuper, Paolo, Ricos, Michael G., Berkovic, Samuel F. and Dibbens, Leanne M. (2014). Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. Annals of Neurology, 75 (5), 782-787. doi: 10.1002/ana.24126

  • Eckhaus, Jazmin, Lawrence, Kate M., Helbig, Ingo, Bui, Minh, Vadlamudi, Lata, Hopper, John L., Scheffer, Ingrid E. and Berkovic, Samuel F. (2013). Genetics of febrile seizure subtypes and syndromes: a twin study. Epilepsy Research, 105 (1-2), 103-109. doi: 10.1016/j.eplepsyres.2013.02.011

  • Vadlamudi, Lata, Dibbens, Leanne M., Lawrence, Kate M., Iona, Xenia, McMahon, Jacinta M., Murrell, Wayne, Mackay-Sim, Alan, Scheffer, Ingrid E. and Berkovic, Samuel F. (2010). Timing of de novo mutagenesis - A twin study of sodium-channel mutations. New England Journal of Medicine, 363 (14), 1335-1340. doi: 10.1056/NEJMoa0910752

  • Helbig, Ingo, Lawrence, Kate, Connellan, Mary, Torn-Broers, Yvonne, Vadlamudi, Lata, Eckhaus, Jazmin, Milne, Roger, Hopper, John and Berkovic, Samuel (2008). Obstetric events as a risk factor for febrile seizures: A community-based twin study. Twin Research and Human Genetics, 11 (6), 634-640. doi: 10.1375/twin.11.6.634

  • Helbig, Ingo, Matigian, Nicholas A., Vadlamudi, Lata, Lawrence, Kate M., Bayly, Marta A., Bain, Sharon M., Diyagama, Dileepa, Scheffer, Ingrid E., Mulley, John C., Holloway, Andrew J., Dibbens, Leanne M., Berkovic, Samuel F. and Hayward, Nicholas K. (2008). Gene expression analysis in absence epilepsy using a monozygotic twin design. Epilepsia, 49 (9), 1546-1554. doi: 10.1111/j.1528-1167.2008.01630.x

  • Berkovic, Samuel F., Dibbens, Leanne M., Oshlack, Alicia, Silver, Jeremy D., Katerelos, Marina, Vears, Danya F., Lüllmann-Rauch, Renate, Blanz, Judith, Zhang, Ke Wei, Stankovich, Jim, Kalnins, Renate M., Dowling, John P., Andermann, Eva, Andermann, Frederick, Faldini, Enrico, D'Hooge, Rudi, Vadlamudi, Lata, Macdonell, Richard A., Hodgson, Bree L., Bayly, Marta A., Savige, Judy, Mulley, John C., Smyth, Gordon K., Power, David A., Saftig, Paul and Bahlo, Melanie (2008). Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis. The American Journal of Human Genetics, 82 (3), 673-684. doi: 10.1016/j.ajhg.2007.12.019

  • McRae, A. F., Matigian, N. A., Vadlamudi, L., Mulley, J. C., Mowry, B., Martin, N. G., Berkovic, S. F., Hayward, N. K. and Visscher, P. M. (2007). Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines. Human Molecular Genetics, 16 (4), 364-373. doi: 10.1093/hmg/ddl456

  • Jansen, F. E., Sadleir, L. G., Harkin, L. A., Vadlamudi, L., McMahon, J. M., Mulley, J. C., Scheffer, I. E. and Berkovic, S. F. (2006). Severe myoclonic epilepsy of infancy (Dravet syndrome): Recognition and diagnosis in adults. Neurology, 67 (12), 2224-2226. doi: 10.1212/01.wnl.0000249312.73155.7d

  • Vadlamudi, L., Vears, D. F., Hughes, A., Pedagogos, E. and Berkovic, S. F. (2006). Action myoclonus–renal failure syndrome: A cause for worsening tremor in young adults. Neurology, 67 (7), 1310-1311. doi: 10.1212/01.wnl.0000238424.23177.5e

  • Vadlamudi, Lata, Kjeldsen, Marianne J., Corey, Linda A., Solaas, Marit H., Friis, Mogen L., Pellock, John M., Nakken, Karl O., Milne, Roger L., Sceffer, Ingrid E., Harvey, A. Simon, Hopper, John L. and Berkovic, Samuel F. (2006). Analyzing the etiology of benign rolandic epilepsy: A multicenter twin collaboration. Epilepsia, 47 (3), 550-555. doi: 10.1111/j.1528-1167.2006.00466.x

  • Vadlamudi, L., Hatton, R., Byth, K., Harasty, J., Vogrin, S., Cook, M. J. and Bleasel, A. F. (2006). Volumetric analysis of a specific language region – the planum temporale. Journal of Clinical Neuroscience, 13 (2), 206-213. doi: 10.1016/j.jocn.2005.03.026

  • Vadlamudi, Lata, Harvey, A. Simon, Hopper, John L., Scheffer, Ingrid E. and Berkovic, Samuel F. (2005). Reply: Genetic influence on rolandic epilepsy. Annals of Neurology, 57 (3), 465-465. doi: 10.1002/ana.20398

  • Vadlamudi, Lata, So, Elson L., Worrell, Gregory A., Mosewich, Russell K., Cascino, Gregory D., Meyer, Fredic B. and Lesnick, Timothy G. (2004). Factors underlying scalp‐EEG interictal epileptiform discharges in intractable frontal lobe epilepsy. Epileptic Disorders, 6 (2), 89-95.

  • Vadlamudi, L., Andermann, E., Lombroso, C. T. and et al. (2004). Epilepsy in twins: Insights from unique historical data of William Lennox. Neurology, 62 (7), 1127-1133. doi: 10.1212/01.WNL.0000118201.89498.48

  • Vadlamudi, Lata, Harvey, Simon A., Connellan, Mary M., Milne, Roger L., Hopper, J. L., Scheffer, I. E. and Berkovic, S. F. (2004). Is benign Rolandic epilepsy genetically determined?. Annals of Neurology, 56 (1), 129-132. doi: 10.1002/ana.20153

  • Vadlamudi, L., Westmoreland, B. F., Klass, D. W. and Parisi, J. E. (2003). Electroencephalographic findings in Kufs disease. Clinical Neurophysiology, 114 (9), 1738-1743. doi: 10.1016/S1388-2457(03)00111-1

  • Vadlamudi, L., Scheffer, I. E. and Berkovic, S. F. (2003). Genetics of temporal lobe epilepsy. Journal of Neurology, Neurosurgery and Psychiatry, 74 (10), 1359-1361. doi: 10.1136/jnnp.74.10.1359

  • Vadlamudi, Lata and Wijdicks, Eelco F.M. (2002). Multifocal myoclonus due to verapamil overdose. Neurology, 58 (6), 984-985. doi: 10.1212/WNL.58.6.984

  • Mitchell, S. J., Benson, M., Vadlamudi, L. and Miller, P. (2000). Cerebral arterial gas embolism by helium: An unusual case successfully treated with hyperbaric oxygen and lidocaine. Annals of Emergency Medicine, 35 (3), 300-303. doi: 10.1016/S0196-0644(00)70086-2

  • Vadlamudi, L., Galton, C. J., Jeavons, S. J., Tannenberg, A. E. G. and Boyle, R. S. (2000). Rasmussen's syndrome in a 54 year old female: more support for an adult variant. Journal of Clinical Neuroscience, 7 (2), 154-156. doi: 10.1054/jocn.1999.0173

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

PhD and MPhil Supervision

Completed Supervision